[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"egfr-gene-mutation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:egfr-gene-mutation":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,21,0,[8,39,70,101,129,161,185,214,261,285,307,334,359,384,405,430,453,475,498,522,546],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":23,"conditions":24,"keywords":4,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":28,"lastUpdatePostDateStruct":29,"startDateStruct":32,"completionDateStruct":34,"leadSponsor":36,"locationsCount":4},"100053582","in-vitro-nsclc-egfr-mutant-models-for-drug-sensitivity-testing-100053582",false,"NCT07697716","In Vitro NSCLC EGFR-Mutant Models for Drug Sensitivity Testing","Targeting EGFR in Lung Cancer: Role of EGFR Mutation State and Bypass Routes in Drug Response and Resistance","PRECISE-EGFR","Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Diagnosis of non-small cell lung cancer (NSCLC), regardless of the line of treatment.\n* Documented presence of an EGFR mutation.\n* Availability of residual biological material obtained from diagnostic or therapeutic procedures performed as part of routine clinical practice.\n* Signed written informed consent for study participation.\n\nExclusion Criteria:\n\n* Patients who have not provided written informed consent will be excluded from the study.","ALL","18 Years",{"count":20,"type":21},30,"ESTIMATED","OBSERVATIONAL","The PRECISE-EGFR study is a prospective, observational project designed to generate patient-derived in vitro models (cell cultures and organoids) from individuals with non-small cell lung cancer (NSCLC) carrying EGFR mutations. These models will be used to evaluate sensitivity to different anti-EGFR therapies and explore mechanisms of drug resistance.\n\nUsing residual biological samples collected during routine clinical practice, the study will not interfere with patient care. Researchers will also compare the molecular characteristics of the models with the original tumors to ensure reliability.\n\nThe overall aim is to improve precision oncology approaches, identifying the most effective treatments for specific EGFR mutation subtypes while minimizing toxicity and resistance.",[25,26],"Carcinoma, Non-Small-Cell Lung","EGFR Gene Mutation","NOT_YET_RECRUITING","2026-07-07",{"date":30,"type":31},"2026-07-13","ACTUAL",{"date":33,"type":21},"2026-09-01",{"date":35,"type":21},"2029-12-31",{"name":37,"class":38},"Fondazione Policlinico Universitario Agostino Gemelli IRCCS","OTHER",{"id":40,"slug":41,"hasResults":11,"nctId":42,"briefTitle":43,"officialTitle":44,"acronym":45,"eligibilityCriteria":46,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":47,"enrollmentInfo":48,"targetDuration":4,"studyType":50,"phases":51,"briefSummary":53,"conditions":54,"keywords":56,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":64,"completionDateStruct":66,"leadSponsor":68,"locationsCount":69},"100635082","phase-2-a-phase-ii-study-of-sacituzumab-tirumotecan-in-combination-with-furmonertinib-in-patients-with-non-squamous-non-small-cell-lung-cancer-who-have-progressed-after-egfr-tki-and-platinum-based-chemotherapy-100635082","NCT07548060","A Phase II Study of Sacituzumab Tirumotecan in Combination With Furmonertinib in Patients With Non-squamous Non-Small Cell Lung Cancer Who Have Progressed After EGFR-TKI and Platinum-Based Chemotherapy","Tianjin Medical University Cancer Institute and Hospital","TROP-LUNG","Inclusion Criteria:\n\n* Histologically or cytologically confirmed non-squamous NSCLC that is locally advanced (Stage ⅢB\u002FⅢC) or metastatic (Stage Ⅳ) and not amenable to curative surgery and\u002For curative concurrent\u002Fsequential chemoradiotherapy \\[according to the 8th edition TNM staging system for lung cancer by the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC)\\], with tissue or blood-based genetic testing showing EGFR-sensitive mutations (19del and L858R).\n* Subjects must have received prior EGFR-TKI therapy for locally advanced or metastatic disease and experienced treatment failure (documented radiographic disease progression), and must meet one of the following requirements: a) progressed after first- or second-generation EGFR-TKI, and histologically confirmed T790M-negative after treatment failure; b) progressed after third-generation EGFR-TKI regardless of T790M mutation status; and progressed after platinum-based chemotherapy or have chemotherapy intolerance.\n\nNote: For subjects who have received neoadjuvant or adjuvant EGFR-TKI therapy, if disease progression occurs ≤12 months from the last dose, this EGFR-TKI is considered first-line therapy for locally advanced or metastatic disease.\n\n* Male or female subjects aged ≥18 years and ≤75 years who have signed the informed consent form.\n* ECOG performance status of 0 or 1, with an expected survival \\>6 months.\n* Agree to provide previously stored tumor tissue specimens or undergo biopsy to collect tumor lesion tissue for biomarker analysis.\n* Adequate organ function: Laboratory tests must meet the following requirements: Absolute neutrophil count (ANC) ≥1.5×10\\^9\u002FL, platelet count ≥100×10\\^9\u002FL, hemoglobin ≥90 g\u002FL, white blood cell count ≥3.0×10\\^9\u002FL; Liver function: Total bilirubin \\\u003C1.5× upper limit of normal (ULN), aspartate aminotransferase (AST\u002FSGOT), alanine aminotransferase (ALT\u002FSGPT), and alkaline phosphatase (ALP) ≤2.5×ULN; If liver metastases are present, AST and ALT ≤5.0×ULN; If liver and\u002For bone metastases are present, ALP ≤5.0×ULN. Renal function: Serum creatinine (Scr) ≤1.5×ULN; Urine routine test shows urine protein \\\u003C2(+); If baseline urine protein ≥2(+), 24-hour urine protein quantification must be ≤1.0 g; Coagulation function: International normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5×ULN.\n\nCardiac function: Left ventricular ejection fraction (LVEF) ≥50%.\n\n-Able to communicate effectively with the investigator and comply with study requirements for visits, treatment, laboratory tests, and other relevant regulations.\n\nExclusion Criteria:\n\n* Squamous cell carcinoma (including adenosquamous carcinoma and undifferentiated carcinoma); small cell lung cancer (including combined small cell and non-small cell lung cancer); patients who have previously received systemic therapy (prior adjuvant or neoadjuvant therapy is permitted).\n* Patients with symptomatic brain metastases at the start of treatment (patients with previously treated brain metastases are eligible if asymptomatic brain metastases persist for at least 4 weeks while on stable dose medication).\n* Patients who participated in an interventional oncology clinical trial concurrently during first-line therapy or within 30 days prior to first-line therapy.\n* History of tracheoesophageal fistula, gastrointestinal perforation or fistula, or intra-abdominal abscess within 6 months before treatment initiation.\n* Patients with severe cardiovascular or cerebrovascular diseases, including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction within 6 months before enrollment, and significant vascular disease (including but not limited to aortic aneurysm requiring surgical repair or recent arterial thrombosis); patients with unstable angina, New York Heart Association (NYHA) class ≥II heart failure; mean resting corrected QT interval (QTc) \\>470 ms; any clinically significant resting ECG rhythm, conduction, or morphological abnormalities, such as complete left bundle branch block, third-degree heart block, second-degree heart block, interval \\>250 ms. Any factors increasing the risk of QTc prolongation or arrhythmic events, such as heart failure, electrolyte abnormalities (including: serum\u002Fplasma potassium \\\u003C LLN; serum\u002Fplasma magnesium \\\u003C LLN; serum\u002Fplasma calcium \\\u003C LLN), congenital long QT syndrome, family history of long QT syndrome, or sudden unexplained death in a first-degree relative under 40 years of age, or any concomitant medication known to prolong QT interval and cause torsades de pointes.\n* Uncontrolled systemic diseases as determined by the investigator:\n\n  1. Poorly controlled diabetes (fasting blood glucose ≥10 mmol\u002FL on two consecutive occasions);\n  2. Poorly controlled hypertension (systolic blood pressure \\>160 mmHg and\u002For diastolic blood pressure \\>100 mmHg);\n  3. Presence of symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage (\\>1 time\u002Fweek).\n* History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment, current ILD or non-infectious pneumonitis, or suspected ILD or non-infectious pneumonitis at screening that cannot be ruled out by imaging examination.\n* Clinically significant pulmonary impairment due to concurrent lung disease, including but not limited to any underlying pulmonary disease (such as pulmonary embolism within 3 months before first dosing, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.\n* Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal bleeding.\n* Tumor invasion of surrounding vital organs and vessels (such as heart, esophagus, superior vena cava, etc.) or risk of developing tracheoesophageal fistula or esophagopleural fistula.\n* Toxicities from prior anti-tumor therapy that have not recovered to ≤Grade 1 (based on NCI CTCAE version 5.0 assessment) or to the level specified in inclusion\u002Fexclusion criteria (except for alopecia, fatigue, and other toxicities that the investigator deems pose no safety risk).\n* Known or suspected hypersensitivity to furmonertinib and sacituzumab tirumotecan and\u002For other components of their formulations.\n* Women of childbearing potential or male subjects who are unwilling to use effective contraception during the study or for 6 months after the last dose of study drug.\n* Active hepatitis B (positive hepatitis B surface antigen (HBsAg) requiring HBV-DNA testing; HBV-DNA ≥500 IU\u002FmL or higher than the lower limit of detection, whichever is higher) or hepatitis C (positive hepatitis C antibody and HCV-RNA higher than the lower limit of detection).\n* Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.\n* Other conditions that the investigator considers unsuitable for enrollment in addition to the above situations.","75 Years",{"count":49,"type":21},25,"INTERVENTIONAL",[52],"PHASE2","Efficacy and Safety of Sacituzumab Tirumotecan Combined with Furmonertinib in Patients with Locally Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer Who Have Progressed After EGFR-TKI and Platinum-Based Chemotherapy.",[55,26],"NSCLC Stage IV",[57,58,59],"NSCLC","TROP-2 ADC","EGFR-TKI","RECRUITING","2026-04-20",{"date":63,"type":31},"2026-04-23",{"date":65,"type":31},"2026-02-01",{"date":67,"type":21},"2028-01-22",{"name":44,"class":38},1,{"id":71,"slug":72,"hasResults":11,"nctId":73,"briefTitle":74,"officialTitle":75,"acronym":4,"eligibilityCriteria":76,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":77,"enrollmentInfo":78,"targetDuration":4,"studyType":50,"phases":80,"briefSummary":82,"conditions":83,"keywords":86,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":92,"lastUpdatePostDateStruct":93,"startDateStruct":95,"completionDateStruct":97,"leadSponsor":99,"locationsCount":69},"100534442","nitroglycerin-plus-radiotherapy-versus-conventional-radiotherapy-in-patients-with-lung-cancer-100534442","NCT06238882","Nitroglycerin Plus Radiotherapy Versus Conventional Radiotherapy in Patients With Lung Cancer.","A Phase III Study Comparing Concurrent Nitroglycerin With Radiation Therapy vs Radiation Therapy Alone in Patients With Non-small Cell Lung Cancer With EGFR Mutations and Brain Metastases.","Inclusion Criteria:\n\n* Patients diagnosed with advanced non-small cell lung cancer (which includes de novo stage IIIB-IV, according to the 8th edition AJCC, or recurrent disease), documented by histology and\u002For cytology.\n* Presence of brain metastases, candidates for treatment with holocranial radiation therapy.\n* Documented EGFR sensitivity mutation.\n* Disease measurable by criteria: The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM).\n* 18 years and up.\n* Functional status, by ECOG scale 0-2\n* Life expectancy at least 12 weeks.\n* Not receive vasodilator treatment as calcium channel blockers.\n* Electrocardiogram\n* Neutrophil count 1.5 x 103\u002Fmm3, platelet count \\>100 x (103\u002Fmm3).\n* Serum bilirubin should be 1.5 of the upper normal limit (ULN, upper normal limit).\n* AST and\u002For ALT 2 ULN (or 5 x ULN in patients with liver metastases).\n* Serum creatinine 1.5 (ULN), or creatinine clearance 60ml\u002Fmin.\n* Ability to comply with study and follow-up procedures.\n* Informed written (signed) consent to participate in the study.\n* Have tumor tissue (paraffin blocks from diagnostic biopsy) obtained before systemic treatment\n\nExclusion Criteria:\n\n* Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, ischemic heart disease, liver, kidney disease).\n* Patients with a history of allergy to glyceryl tinistate\n* Any other malignant pathology within the previous 5 years (except for cervical carcinoma in situ or basal-cell skin cancer, treated appropriately).\n* Pregnant and\u002For breastfeeding women.\n* Meningeal carcinomatosis corroborated by cytopathological study.\n\nDisposal Criteria:\n\n* Failure to follow protocol rules.\n* Loss of patient follow-up.\n* Patients who express their desire not to continue the study.\n* Patients with unacceptable toxicity","85 Years",{"count":79,"type":21},74,[81],"NA","The goal of this interventional phase III clinical trial is to evaluate objective intracranial response rate (iORR) after a treatment with total cranial radiation therapy plus concomitant transdermal nitroglycerin (NTG) addition or total cranial radiation therapy only in patients with stage IV non-small cell lung cancer with brain metastases and EGFR mutation. The main questions it aims to answer are:\n\nDetermine progression-free survival (PFS) to CNS and overall survival (OS). Evaluate and compare the quality of life (QoL) of patients during and after treatment.\n\nEvaluate the cognitive function of patients before, during and after treatment. Evaluate treatment-associated toxicity to grade adverse treatment events Evaluation of HIF1α, VEGF and ROS1 in peripheral blood before and after nitroglycerin treatment.\n\nAll participants will have laboratory tests at the beginning and end of radiation therapy. Cranial MRI will be performed prior to treatment and 12 weeks after the end of treatment, then every 16 weeks until intracranial progression. Patients in the interventional group will be given 36 mg patches of transdermal nitroglycerin for 24 hours with a 12-hour rest interval during treatment with radiation therapy. The control group will only receive total cranial radiation therapy at the same doses and with the same schedule.",[84,85,26],"Non-small Cell Lung Cancer","Brain Metastases",[87,88,89,90,91],"Radiation therapy","Nitroglycerin","Brain metastases","EGFR mutation","Non-small cell lung cancer","2026-04-06",{"date":94,"type":31},"2026-04-09",{"date":96,"type":31},"2023-02-23",{"date":98,"type":21},"2027-02-15",{"name":100,"class":38},"Instituto Nacional de Cancerologia de Mexico",{"id":102,"slug":103,"hasResults":11,"nctId":104,"briefTitle":105,"officialTitle":106,"acronym":4,"eligibilityCriteria":107,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":108,"targetDuration":4,"studyType":50,"phases":110,"briefSummary":112,"conditions":113,"keywords":117,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":120,"lastUpdatePostDateStruct":121,"startDateStruct":123,"completionDateStruct":125,"leadSponsor":127,"locationsCount":69},"100530409","phase-1-anti-egfrviii-synnotch-receptor-induced-anti-epha2il-13ralpha2-car-e-sync-t-cells-100530409","NCT06186401","Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2\u002FIL-13Ralpha2 CAR (E-SYNC) T Cells","Phase 1 Study of Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2\u002FIL-13R alpha2 CAR (E-SYNC) T Cells in Adult Participants With EGFRvIII+ Glioblastoma","Inclusion Criteria:\n\n* Inclusion Criteria for Cohort 1:\n\n  1. Age \\>= 18 years.\n  2. Karnofsky performance status (KPS) score of \\>=70.\n  3. All participants must have adequate organ function defined as:\n\n     1. Peripheral absolute neutrophil count \\>=1000\u002Fmm\\^3.\n     2. Platelet count \\>=100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n     3. Absolute lymphocyte count (ALC) \\>= 300\u002FμL and\u002For Cluster of differentiation 3 (CD3) count of \\>=150\u002FμL.\n     4. Creatinine clearance or radioisotope glomerular filtration rate \\>= 50 mL\u002Fmin\u002F1.73m\\^2.\n     5. Total Bilirubin \\\u003C= 1.5 x ULN except for Gilbert's syndrome and\n     6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C= 3x upper limit of normal (ULN).\n     7. Left ventricular ejection fraction (LVEF) \\>= 50% by echocardiogram or multi-gated acquisition scanning (MUGA).\n     8. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \\> 92% while breathing room air.\n  4. Pathological criteria: EGFRvIII+ GBM from most recent surgery, confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using a next-generation sequencing panel.\n  5. MGMT promoter must be unmethylated or with a methylation index \\\u003C 3.\n  6. Must have completed at least standard of care (SOC) external beam radiotherapy (EBRT) as initial therapy.\n  7. Participants must be anticipated to be able to complete E-SYNC T cell infusion within 12 weeks after completion of EBRT.\n  8. All participants must be off systemic steroids for 3 days or more prior to leukapheresis.\n  9. Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed) and for study treatment.\n\nNOTE: There are two sets of eligibility criteria for Cohort 2. Step 1 defines eligibility for tissue screening and apheresis, and Step 2 defines eligibility for study enrollment and E-SYNC T cell treatment.\n\n* Inclusion Criteria for Cohort 2, Step 1:\n\n  1. Age \\>=18 years.\n  2. KPS score \\>=70.\n  3. All participants must have adequate organ function defined as:\n\n     1. Peripheral absolute neutrophil count \\>=1000\u002Fmm\\^3.\n     2. Platelet count \\>=100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n     3. Absolute lymphocyte count (ALC) \\>= 300\u002FμL and\u002For CD3 count of \\>=150\u002FμL.\n     4. Creatinine clearance or radioisotope glomerular filtration rate \\>= 50 mL\u002Fmin\u002F1.73m\\^2.\n     5. Total Bilirubin \\\u003C= 1.5 x ULN except for Gilbert's syndrome and\n     6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C= 3x upper limit of normal (ULN).\n     7. Left ventricular ejection fraction (LVEF) \\>= 50% by echocardiogram or multi-gated acquisition scanning (MUGA).\n     8. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \\> 92% while breathing room air.\n  4. Pathological criteria: EGFRvIII+ GBM from most recent surgery, as defined by an EGFRvIII + H-score of \\>=250 based on central review.\n  5. All participants must be off systemic steroids for 3 days or more prior to leukapheresis.\n  6. Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed).\n* Inclusion Criteria for Cohort 2, Step 2. Note: Prior to Step 2, participants must have undergone leukapheresis in Step 1. In addition:\n\n  1. KPS score \\>=70.\n  2. Must have received at least SOC EBRT as initial therapy; any number of prior recurrences is allowed.\n  3. Pathological criteria: EGFRvIII+ GBM from most recent surgery, as defined by an EGFRvIII + H-score of \\>=250 based on central review.\n  4. Must have radiographic progression consistent with the Response assessment in neuro-oncology criteria (RANO) criteria for progressive disease (PD)\n  5. Recurrence must be surgically amenable, with expectation for ability to resect at least 500mg of tumor tissue\n  6. Participants with reproductive potential agree to use reliable and double barrier method of contraception during the study and for at least 6 months after the last study intervention, including refraining from donating sperm during this period.\n  7. Females of childbearing potential must have a negative serum beta-Human Chorionic Gonadotropin (hCG) pregnancy test prior to receiving study interventions.\n  8. All participants must have adequate organ function defined as:\n\n     1. Peripheral absolute neutrophil count \\>=1000\u002Fmm\\^3.\n     2. Platelet count \\>=100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n     3. Absolute lymphocyte count (ALC) \\>= 300\u002FμL and\u002For CD3 count of \\>=150\u002FμL.\n     4. Creatinine clearance or radioisotope glomerular filtration rate \\>= 50 mL\u002Fmin\u002F1.73m\\^2.\n     5. Total Bilirubin \\\u003C= 1.5 x ULN except for Gilbert's syndrome and\n     6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C= 3x upper limit of normal (ULN).\n     7. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) have to be within normal limits, unless the participant has been therapeutically anticoagulated for previous venous thrombosis.\n     8. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \\> 92% while breathing room air.\n     9. Adequate cardiac function, confirmed within the last 12 months, defined as left ventricular ejection fraction (LVEF) \\>= 40% by echocardiogram or multi-gated acquisition scanning (MUGA).\n  9. Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed).\n\nExclusion Criteria:\n\n* Exclusion Criteria for Cohort 1\n\n  1. Participant who has been treated with any investigational agents and chemotherapy targeting GBM \\\u003C= 4 weeks prior to date of study registration. Exceptions to this include: must be \\>=23 days from last dose of temozolomide (TMZ) or radiotherapy, mush be \\>= 6 weeks from last dose of nitrosourea.\n  2. Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of eligibility confirmation.\n  3. Known addiction to alcohol or illicit drugs.\n  4. Prior treatment with any Epithelial Growth Factor Receptor (EGFR)-targeting therapy.\n  5. Participants with leptomeningeal dissemination.\n  6. Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy. Participants who are currently using non-systemic steroids (e.g., inhaled, intranasal, ocular, topical) are not excluded from the study.\n  7. Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.\n  8. Participants who have received prior solid organ or bone marrow transplantation.\n  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, second cancer currently receiving active treatment or anticipated to receive treatment within the next year, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n  10. Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.\n* Exclusion Criteria for Step 1 for Cohort 2\n\n  1. Participant who has been treated with any investigational agents or chemotherapy targeting GBM \\\u003C=4 weeks prior to date of study registration. Exceptions to this include: must be\\>= 23 days from last dose of TMZ or radiotherapy, must be\\>=6 weeks from last dose of nitrosourea.\n  2. Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of Step 1 eligibility confirmation.\n  3. Uncontrolled active infection.\n  4. Participants with a known disorder that affects their immune system, such as HIV or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy.\n\n     Participants who are currently using non-systemic steroids (e.g., inhaled, intranasal, ocular, topical) are not excluded from the study.\n  5. Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.\n  6. Known addiction to alcohol or illicit drugs.\n* Exclusion Criteria for Step 2 for Cohort 2\n\nPrior to Step 2, participants must have undergone leukapheresis in Step 1. In addition:\n\n1. Prior treatment with any EGFR-targeting therapy\n2. Participant who has been treated with any investigational agents or chemotherapy targeting GBM \\\u003C= 4 weeks prior to date of study registration. Exceptions to this include: must be \\>= 23 days from last dose of TMZ or radiotherapy, must be \\>= 6 weeks from last dose of nitrosourea.\n3. Participants with imaging or clinical evidence of uncontrolled tumor mass effect; the assessment of mass effect will be made by the Investigators.\n4. Participants with leptomeningeal dissemination.\n5. Participants with a known disorder that affects their immune system, such as HIV or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy.\n\n   Participants who are currently using inhaled, intranasal, ocular, topical, or other non-oral or non-IV steroids are not necessarily excluded from the study.\n6. Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.\n7. Participants who have received prior solid organ or bone marrow transplantation.\n8. Female participants who are pregnant or breast-feeding.\n9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, second cancer currently receiving active treatment or anticipated to receive treatment within the next year, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n10. Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.",{"count":109,"type":21},20,[111],"PHASE1","This phase I trial tests the safety, side effects, and best dose of E-SYNC chimeric antigen receptor (CAR) T cells after lymphodepleting chemotherapy in treating patients with EGFRvIII positive (+) glioblastoma. Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so the CAR T cells will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine before treatment with CAR T cells may make the CAR T cells more effective.",[26,114,115,116],"Glioblastoma","MGMT-Unmethylated Glioblastoma","Recurrent Glioblastoma",[118,119],"Immunotherapy","CAR T Therapy","2026-03-12",{"date":122,"type":31},"2026-03-16",{"date":124,"type":31},"2024-04-30",{"date":126,"type":21},"2027-12-31",{"name":128,"class":38},"Hideho Okada, MD, PhD",{"id":130,"slug":131,"hasResults":11,"nctId":132,"briefTitle":133,"officialTitle":133,"acronym":4,"eligibilityCriteria":134,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":135,"enrollmentInfo":136,"targetDuration":4,"studyType":50,"phases":138,"briefSummary":139,"conditions":140,"keywords":145,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":152,"lastUpdatePostDateStruct":153,"startDateStruct":155,"completionDateStruct":157,"leadSponsor":159,"locationsCount":4},"100628445","phase-1-an-open-label-single-arm-dose-escalation-phase-i-study-evaluating-the-safety-tolerability-and-preliminary-efficacy-of-edb-102-in-patients-with-egfr-l858r-mutant-third-generation-tki-resistant-advanced-non-small-cell-lung-cancer-with-liver-metastases-100628445","NCT07461727","An Open-Label, Single-Arm, Dose-Escalation Phase I Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of EDB-102 in Patients With EGFR L858R-Mutant, Third-Generation TKI-Resistant Advanced Non-Small Cell Lung Cancer With Liver Metastases","Inclusion Criteria:\n\n1. Age ≥18 and ≤75 years, any sex.\n2. Histologically or cytologically confirmed, unresectable locally advanced or metastatic (stage IV) non-small cell lung cancer (NSCLC)\n3. Prior treatment with at least one third-generation EGFR-TKI (e.g., osimertinib) with radiologically confirmed disease progression according to RECIST 1.1 or intolerance, and no concomitant anticancer therapy during this period.\n4. Availability of tumor tissue obtained after progression on third-generation EGFR-TKI, with EGFR L858R mutation confirmed in the post-progression tumor tissue or blood sample by central laboratory- or study site-validated methods (e.g., WES or RNAseq).\n5. At least one measurable hepatic lesion per RECIST 1.1, confirmed by biopsy, with the EGFR L858R mutation verified in the lesion by central laboratory- or study site-validated methods (e.g., WES or RNAseq).\n6. ECOG performance status of 0 or 1.\n7. Adequate organ and bone marrow function: a) Hematologic: within 14 days prior to enrollment and without recent transfusion or growth factor therapy: ANC ≥1.5×10⁹\u002FL, Hb ≥90 g\u002FL, PLT ≥75×10⁹\u002FL, WBC \\>3.0×10⁹\u002FL. b) Hepatic: TBIL ≤1.5×ULN, ALT ≤5×ULN, AST ≤5×ULN. c) Renal: serum creatinine ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL\u002Fmin. d) Coagulation: PT ≤1.5×ULN, APTT ≤1.5×ULN, INR ≤1.5×ULN.\n8. Ability and willingness to provide written informed consent, comply with study procedures, and cooperate with study personnel.\n\nExclusion Criteria:\n\n1. Prior exposure to any gene-editing therapies (e.g., CRISPR, TALEN, ZFN)\n2. Receipt of chemotherapy, radiotherapy, biologic therapy, endocrine therapy, targeted therapy, immunotherapy, or other anticancer agents within 4 weeks prior to the first dose of study drug. For oral fluoropyrimidines or small-molecule targeted agents, the washout period is 2 weeks or 5 half-lives of the drug, whichever is longer\n3. Receipt of any investigational, unapproved therapy within 4 weeks prior to the first dose of study drug.\n4. Presence of other known driver gene alterations conferring TKI resistance, excluding EGFR mutations, unless these occur as co-mutations, including: Bypass pathway activation: High-level MET amplification: detected by WES (gene copy number \\>5) or FISH (MET\u002FCEP7 ratio ≥2.0). High-level HER2 amplification: detected by ISH (gene copy number ≥6 per nucleus, HER2\u002FCEP17 ratio ≥2.0). Other acquired resistance driver mutations: Newly emerged confirmed resistance mutations, e.g., KRAS or BRAF-V600E. Activating mutations in PI3K\u002FAKT\u002FmTOR pathway genes (e.g., PIK3CA). Loss of primary EGFR mutation: absence of the original EGFR L858R mutation in post-resistance tumor tissue.\n5. Known allergy or adverse reaction to any lipid nanoparticle (LNP) components.\n6. Uncontrolled hypertension (systolic BP \\>150 mmHg and\u002For diastolic BP \\>100 mmHg despite regular antihypertensive therapy) or history of hypertensive crisis or hypertensive encephalopathy.\n7. Liver disease, including cirrhosis, hepatitis, or history of hepatitis B or C infection.\n8. Unstable angina or acute myocardial infarction, or history of these events within the past 6 months.\n9. History of malignancy within the past 5 years, except for treated basal cell carcinoma, cutaneous squamous cell carcinoma, cervical cancer, or gastrointestinal cancers.\n10. Pregnant, breastfeeding, positive pregnancy test, or unwillingness to use contraception in premenopausal women. Women are considered postmenopausal if amenorrheic for ≥2 years. Male patients unwilling to use contraception during the study are also excluded.\n11. Leptomeningeal, brainstem, or spinal metastases, or active CNS metastases with compression. Subjects with previously treated brain metastases may participate if clinically stable ≥4 weeks prior to first study drug administration and off corticosteroids for ≥14 days.\n12. Any condition deemed by the investigator to make the subject unsuitable for participation in the study.","65 Years",{"count":137,"type":21},15,[111],"The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of EDB-102 Injection in patients with advanced non-small cell lung cancer (NSCLC) who have liver metastases. The study specifically targets patients harboring the EGFR-L858R mutation who have disease progression after treatment with third-generation EGFR tyrosine kinase inhibitors (TKIs, e.g., osimertinib).\n\nEDB-102 is a novel in vivo gene-editing therapy. It consists of CRISPR-Cas9 mRNA and a single-guide RNA (sgRNA) encapsulated in lipid nanoparticles (LNPs). The drug is designed to specifically identify and disrupt the mutant EGFR-L858R gene in tumor cells, thereby inhibiting tumor growth. Due to the liver-targeting properties of the LNP carrier, this therapy is particularly aimed at patients with liver metastases.\n\nThis is a Phase I, open-label, dose-escalation study. Participants will receive a single intravenous (IV) infusion of EDB-102. The study will follow a \"3+3\" design to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D). Participants will be monitored for adverse events, and tumor biopsies will be collected to assess the gene-editing efficiency of the drug.",[141,142,143,26,144],"Non-Small Cell Lung Cancer","Metastatic Non-small Cell Lung Cancer","Liver Metastases","EGFR L858R",[146,147,144,148,149,150,151],"EDB-102","CRISPR-Cas9","Lipid Nanoparticles (LNP)","In vivo Gene Editing","TKI Resistance","Osimertinib Resistance","2026-03-05",{"date":154,"type":31},"2026-03-10",{"date":156,"type":21},"2026-02-10",{"date":158,"type":21},"2029-01-31",{"name":160,"class":38},"Cancer Institute and Hospital, Chinese Academy of Medical Sciences",{"id":162,"slug":163,"hasResults":11,"nctId":164,"briefTitle":165,"officialTitle":166,"acronym":4,"eligibilityCriteria":167,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":77,"enrollmentInfo":168,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":170,"conditions":171,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":176,"lastUpdatePostDateStruct":177,"startDateStruct":179,"completionDateStruct":181,"leadSponsor":183,"locationsCount":69},"100289013","early-rebiopsy-to-identify-biomarkers-of-tumor-cell-survival-following-egfr-alk-ros1-or-braf-tki-therapy-100289013","NCT03042221","Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy","Early Rebiopsy to Identify Mechanisms and Biomarkers of Tumor Cell Survival Following Systemic Therapy for Lung Cancer","Inclusion Criteria:\n\nTargetable Oncogene - Biopsy Cohort (includes blood draw)\n\n1. Carry a diagnosis of locally advanced or stage IV NSCLC responsive to targeted therapies (per current NCCN guidelines)\n2. Aged 18 years or older\n3. ECOG 0-2\n4. Have a histologically confirmed diagnosis of NSCLC harboring an activating mutation responsive to targeted therapy (per NCCN guidelines)\n5. No prior systemic therapy for locally advanced or metastatic disease.\n6. Planned treatment with targeted therapy specific to the oncogene driver mutation.\n7. Patients must have at least one site of measurable disease ≥ 2cm.\n8. Primary disease site or site of metastatic disease must be amenable to biopsy.\n9. Patients must have the ability to understand and willingness to sign an informed consent document.\n\nTargetable Oncogene - Blood Draw Only Cohort\n\n1. Carry a diagnosis of locally advanced or stage IV NSCLC responsive to targeted therapy (per NCCN guidelines)\n2. Aged 18 years or older\n3. ECOG 0-2\n4. Have a histologically confirmed diagnosis of NSCLC harboring an activating mutation responsive to targeted therapy (per NCCN guidelines)\n5. No prior systemic therapy or radiotherapy for metastatic lung cancer (surgery alone permitted)\n6. Planned treatment with targeted therapy specific to the oncogene driver mutation.\n7. Declines repeat biopsy option or does not have tumor site amenable to biopsy.\n8. Patients must have the ability to understand and willingness to sign an informed consent document.\n\nImmunotherapy Cohort - Blood Draw Only\n\n1. Have a histologically confirmed diagnosis of locally advanced or stage IV NSCLC without a treatable activating mutation that would be amenable to targeted therapy AND planned first line treatment with immunotherapy or chemotherapy plus immunotherapy.\n2. Aged 18 years or older\n3. ECOG 0-2\n4. No prior systemic therapy or radiation therapy for lung cancer (surgery alone permitted)\n5. Patients must have the ability to understand and willingness to sign an informed consent document.\n\nExclusion Criteria:\n\nTargetable Oncogene - Biopsy Cohort (includes blood draw)\n\n1. Concurrent health problem which would preclude tissue biopsy (e.g. hemophilia or other bleeding predisposition).\n2. Patients whose only biopsy source would involve sampling an anatomic area that carries an unacceptably high procedural risk (e.g. pericardium or kidney) as deemed by the treating physician or by a proceduralist performing the biopsy.\n3. Patients whose only biopsy source involves a sample that may not be evaluable due to insufficient genomic material (such as cerebrospinal or ascitic fluid) as deemed by the treating physician. .\n\nTargetable Oncogene Cohort and Immunotherapy Cohort - Blood Draw Only\n\n1. Planned follow up on therapy outside of the University of Colorado Health System\n2. Unwillingness to allow for residual clinical biopsy specimens to be utilized in this study.",{"count":169,"type":21},100,"A comparison of baseline tumor characteristics in oncogene-driven cancers to tumor characteristics after early response to Tyrosine Kinase Inhibitor (TKI) targeted treatment will allow identification of early adaptive mechanisms of cell survival. This will facilitate targeting and termination of these survival\u002F resistance pathways before they develop with rational combinations of therapeutic agents to improve outcomes.",[172,141,26,173,174,175],"Non-Small Cell Carcinoma of Lung, TNM Stage 4","ALK Gene Mutation","ROSE Cluster 1","BRAF V600E","2026-02-18",{"date":178,"type":31},"2026-02-20",{"date":180,"type":31},"2016-05-10",{"date":182,"type":21},"2027-09-30",{"name":184,"class":38},"University of Colorado, Denver",{"id":186,"slug":187,"hasResults":11,"nctId":188,"briefTitle":189,"officialTitle":189,"acronym":190,"eligibilityCriteria":191,"healthyVolunteers":192,"sex":17,"minAge":193,"maxAge":194,"enrollmentInfo":195,"targetDuration":4,"studyType":50,"phases":197,"briefSummary":198,"conditions":199,"keywords":201,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":204,"lastUpdatePostDateStruct":205,"startDateStruct":207,"completionDateStruct":209,"leadSponsor":211,"locationsCount":213},"100571156","equal-egfr-ctdna-quantative-assessment-for-lung-cancer-screening-in-asian-and-latinx-populations-100571156","NCT06716580","EQUAL: EGFR ctDNA QUantative Assessment for Lung Cancer Screening in Asian and Latinx Populations","EQUAL","Inclusion Criteria (Aims 1, 2, and 3) for Group 1 (50 through 80 years of age):\n\n* Non-tobacco using (currently)\n* Self-identify as East Asian (including Southeast Asian) or Hispanic\u002FLatinx.\n* East Asian includes those who self-identify as Chinese, Japanese, Korean, Taiwanese, Malaysian\n* Southeast Asian includes those who self-identify as Cambodian, Thai, Vietnamese, Filipino\n* Latinx includes those who self-identify as a person of Central or South American and the Caribbean including, Cuban, Puerto Rican, and Dominican culture or origin, excluding individuals originating from Spain\n* Aims 1 and 2: Able to complete and understand the study's informed consent in English, Mandarin, Cantonese, Japanese, Korean, Vietnamese, Spanish, Portuguese, or Cape Verdean\n* Aim 3: Able to complete and understand the study's informed consent and participate in a focus group in English, Mandarin, Vietnamese, or Spanish.\n\nInclusion Criteria (Aims 1, 2, and 3) for Group 2 (40 through 49 years of age):\n\n* Non-tobacco using (currently)\n* Self-identify as East Asian (including Southeast Asian) or Latinx, if any of the following criteria are met:\n\n  * Family history of EGFR positive LC L858R or exon 19\n  * Personal history of remote cancer that is not LC or other thoracic malignancies, including thymoma, thymic carcinoma, or sarcoma, as long as it was resolved over 5 years ago\n  * History of TB, asthma requiring daily inhaled corticosteroids or chronic bronchitis\n  * Symptoms of lung cancer for the past month, including hemoptysis, unexplained weight loss, voice hoarseness, cough or worsening cough, dyspnea or worsening dyspnea\n* Excluding individuals who concurrently present with fever, covid\u002Finfluenza\u002FRSV\u002Fadenovirus infection, runny nose, sore throat, productive cough with green or yellow sputum\n* Aims 1 and 2: Able to complete and understand the study's informed consent in English, Mandarin, Cantonese, Japanese, Korean, Vietnamese, Spanish, Portuguese, or Cape Verdean\n* Aim 3: Able to complete and understand the study's informed consent and participate in a focus group in English, Mandarin, Vietnamese, or Spanish.\n\nExclusion Criteria (Aims 1, 2, and 3) for Groups 1 and 2:\n\n* Having had a chest CT scan in the last 3 years or having an anticipated chest CT scan during the enrollment period.\n* Having a current cancer or history of cancer within the last 5 years, excluding localized non-melanoma skin cancer and breast ductal carcinoma in situ.\n* More than 400 lifetime cigarettes (i.e., 20 packs) of smoking or tobacco use\n* Adults unable to provide informed consent\n* Individuals \\\u003C40 years of age\n* Prisoners\n* Pregnant women\n* Personal diagnosis of lung cancer\n* Not able to be compliant with study requirements",true,"40 Years","80 Years",{"count":196,"type":21},1000,[81],"This research study is studying a new blood test to screen for Epidermal Growth Factor Receptor (EGFR) positive lung cancer in healthy individuals at risk for the disease and who cannot undergo regular lung cancer screening.\n\nThe name of the test used in this research study is:\n\n-Circulating free DNA (cfDNA) Assay",[200,26],"Lung Cancer",[200,26,202,203],"EGFR-related lung cancer","EGFR positive lung cancer","2025-12-08",{"date":206,"type":31},"2025-12-10",{"date":208,"type":31},"2025-04-01",{"date":210,"type":21},"2030-09-01",{"name":212,"class":38},"Dana-Farber Cancer Institute",6,{"id":215,"slug":216,"hasResults":11,"nctId":217,"briefTitle":218,"officialTitle":219,"acronym":220,"eligibilityCriteria":221,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":222,"targetDuration":4,"studyType":50,"phases":224,"briefSummary":225,"conditions":226,"keywords":242,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":250,"lastUpdatePostDateStruct":251,"startDateStruct":253,"completionDateStruct":255,"leadSponsor":257,"locationsCount":260},"100299221","phase-2-apl-101-study-of-subjects-with-nsclc-with-c-met-exon-14-skip-mutations-and-c-met-dysregulation-advanced-solid-tumors-100299221","NCT03175224","APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors","Phase 1 \u002F 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects With Non-Small Cell Lung Cancer With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors","SPARTA","Major Inclusion Criteria:\n\n1. Men and women 18 years of age or older.\n2. 9 cohorts will be enrolled:\n\n   * Cohort A1 \u002F Exon 14 NSCLC MET inhibitor naive in first line: Histologically or cytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies; unresectable or metastatic disease (Stage 3b\u002F4); treatment-naive subjects in first line; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort A2 \u002F Exon 14 NSCLC - MET inhibitor naïve: Histologically or cytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies; unresectable or metastatic disease (Stage 3b\u002F4); pretreated subjects refractory to or intolerant of standard therapies with no more than three lines of prior therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort B \u002F Exon 14 NSCLC MET inhibitor experienced: ENROLLMENT COMPLETED\n   * Cohort C \u002F MET amplification basket tumor types excluding primary CNS tumors: Any solid tumor type regardless of histology excluding primary CNS tumors, with MET amplification; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort C1 \u002F MET amplification and wild-type EGFR NSCLC: NSCLC regardless of histology, harboring MET amplification and wild-type EGFR; unresectable or metastatic disease, previously untreated or treated with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort C2 \u002F EGFR positive NSCLC with acquired MET amplification (APL-101 Add-on Therapy): Unresectable or metastatic NSCLC regardless of histology, harboring EGFR activating mutations with acquired MET-Amplification as resistance mechanism to the EGFR-I; developed resistance to first-line EGFR-inhibitor therapy after an initial response (documented PR for at least 12 weeks); radiological documentation of disease progression per RECIST on first-line EGFR inhibitor therapy; currently on an EGFR-inhibitor therapy and agrees to receive APL-101 as an add-on therapy during the study; no history of interstitial lung disease (ILD)\u002Fpneumonitis, Grade ≥3 liver toxicity or QT prolongation with EGFR-I therapy; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort D \u002F MET fusion basket tumor types excluding primary CNS tumors: any solid tumor type regardless of histology excluding primary CNS tumors; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort E \u002F Primary CNS tumors with MET alterations: subjects with primary CNS tumors who meet inclusion criteria of MET dysregulations defined as single or co-occurred MET fusion including PTPRZ1-MET (ZM) fusion, MET Exon 14 skipping mutations, or MET amplification; refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations; neurological symptoms controlled on a stable\u002Fdecreasing dose of steroids for at least 2 weeks before C1D1\n   * Cohort F \u002F Basket tumor types harboring wild-type MET with over-expression of HGF and MET: any solid tumor type regardless of histology harboring wild-type MET with overexpression of HGF and MET; Unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n3. Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is allowed.\n4. Presence of ≥1 measurable lesion (scan done ≤28 days of C1D1) to serve as target lesion according to relevant criteria\n5. ECOG performance status of 0-1. For subjects with primary CNS tumors, KPS score ≥70.\n6. Acceptable organ function\n7. For all prior anticancer treatment, a duration of 30 days or 5 half-lives of the agents used, whichever is shorter, must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria prior to the first dose of study treatment. Palliative radiotherapy to non-target lesions should be completed within 2 weeks prior to APL-101 administration.\n8. Adequate cardiac function\n9. Women of child-bearing potential must have a negative serum or Beta-hCG at screening or evidence of surgical sterility or evidence of post-menopausal status\n10. No planned major surgery within 4 weeks of first dose of APL-101\n11. Expected survival (life expectancy) ≥ 3 months from C1D1\n12. Provision of sample; e.g. archival or a fresh tumor biopsy sample (if safe and feasible) either from the primary or a metastatic site) or liquid biopsy sample (if tumor tissue is insufficient or lacking, and approved by the sponsor) is required for prospective central lab confirmation for study entry (subjects with previously confirmed molecular status by the Sponsor designated central lab or FDA approved NGS based MET testing may be exempted, subjected to Sponsor approval.\n\nMajor Exclusion Criteria:\n\n1. Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.\n2. Known actionable mutation\u002Fgene rearrangement of EGFR (except for NSCLC subjects in Cohort C and C-2), ALK, ROS1, RET, NTRK, KRAS, and BRAF.\n3. Use or intended use of any other investigational product, including herbal medications, through Study Treatment Termination.\n4. Active uncontrolled systemic bacterial, viral, or fungal infection or clinically significant, active disease process, which in the opinion of the investigator makes the risk: benefit unfavorable for the participation of the trial.\n5. Life-threatening illness, significant organ system dysfunction or comorbid conditions, or other reasons that, in the investigator's opinion, could compromise the subject's safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of APL-101.\n6. Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101, symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at screening, or concurrent treatment with a medication that is a known risk for prolonging the QT interval. Chronic controlled atrial fibrillation is not excluded.\n7. Historical seropositive results consistent with active infection for hepatitis C virus (HCV) or hepatitis B virus (HBV) with high viral loads not actively managed with antiviral therapy and human immunodeficiency virus (HIV) positive subjects who are not clinically stable or controlled on their medication (asymptomatic subjects with CD4+ T-cell (CD4+) counts ≥ 350 cells\u002FμL and have not had an opportunistic infection within the past 12 months prior to first dose of APL-101 would be eligible for study entry. If history is unclear, relevant test(s) at Screening will be required to confirm eligibility.\n8. Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments.\n9. Unable to swallow orally administered medication whole.\n10. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption\n11. Women who are breastfeeding\n12. History of another malignancy within 3 years prior to C1D1. A subject with the following malignancies is allowed if considered cured or unlikely to recur within 3 years:\n\n    1. Carcinoma of the skin without melanomatous features.\n    2. Curatively treated cervical carcinoma in situ.\n    3. Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in situ (T1s), thyroid papillary cancer with prior treatment, prostate cancer which has been surgically or medically treated and not likely to recur within 3 years.\n13. Subjects who are unable or unwilling to discontinue excluded medications (drugs with known QTc risk and known strong cytochrome P450 \\[CYP\\]3A4 inducer and\u002For strong inhibitors) for at least 5 half-lives prior to first dose of study drug. Subjects may qualify if such medication(s) can be safely replaced with alternate medications with less risk of drug-drug interaction.\n14. Subjects with active COVID-19 infection.\n15. Symptomatic and\u002For neurologically unstable CNS metastases, or who require an increase in steroid dose to control CNS disease. Subjects who have been receiving a stable steroid dose for at least 2 weeks prior to C1D1 may be allowed.",{"count":223,"type":21},497,[52],"To assess:\n\n* efficacy of APL-101 as monotherapy for the treatment of NSCLC harboring MET Exon 14 skipping mutations, NSCLC harboring MET amplification, solid tumors harboring MET amplification, solid tumors harboring MET fusion, primary CNS tumors harboring MET alterations, solid tumors harboring wild-type MET with overexpression of HGF and MET\n* efficacy of APL-101 as an add-on therapy to EGFR inhibitor for the treatment of NSCLC harboring EGFR activating mutations and developed acquired resistance with MET amplification and disease progression after documented CR or PR with 1st line EGFR inhibitors (EGFR-I)",[227,228,229,230,231,57,200,232,233,26,234,235,236,237,238,239,240,241],"Solid Tumors","Advanced Cancer","Renal Cancer","Gastric Cancer","Gastroesophageal Junction Adenocarcinoma","Brain Tumor","Glioblastoma Multiforme","MET Amplification","HGF","Thyroid Cancer","Pancreatic Cancer","Colon Cancer","MET Alteration","MET Fusion","Exon 14 Skipping",[243,244,245,246,247,248,235,249],"Advanced Solid Tumor","Relapsed Solid Tumor","Recurrent Solid Tumor","cMet exon 14 skipping","cMet fusion","GBM","EGFR positive","2025-06-24",{"date":252,"type":31},"2025-06-27",{"date":254,"type":31},"2017-09-27",{"date":256,"type":21},"2026-11-30",{"name":258,"class":259},"Apollomics Inc.","INDUSTRY",35,{"id":262,"slug":263,"hasResults":11,"nctId":264,"briefTitle":265,"officialTitle":265,"acronym":4,"eligibilityCriteria":266,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":267,"targetDuration":4,"studyType":50,"phases":269,"briefSummary":270,"conditions":271,"keywords":274,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":276,"lastUpdatePostDateStruct":277,"startDateStruct":279,"completionDateStruct":281,"leadSponsor":283,"locationsCount":69},"100533182","phase-2-whole-body-her3-quantification-with-radiolabelled-patritumab-deruxtecan-her3-dxd-petct-100533182","NCT06222489","Whole Body HER3 Quantification With Radiolabelled Patritumab Deruxtecan (HER3-DXd) PET\u002FCT","Inclusion Criteria:\n\n1. Provision of informed consent prior to any study specific procedures.\n2. Have a histologically or cytologically confirmed diagnosis of (locally) advanced stage EGFR mutation positive NSCLC, not amenable for curative intent treatment.\n3. Have measurable disease according to RECIST 1.1.\n4. At least two lesions with a long axis diameter ≥2 cm.\n5. Have received at least one line of EGFR TKI treatment for (locally) advanced stage NSCLC.\n6. In case the tumor is positive for T790M mutation, prior treatment with a third generation EGFR TKI is mandatory.\n7. Patients must be ≥18 years of age.\n8. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 at the time of Screening.\n9. Has adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1, defined as:\n\n   * Platelet count ≥100 000\u002Fmm3 or ≥100 × 109\u002FL (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility)\n   * Hemoglobin (Hgb) ≥9.0 g\u002FdL or 5.6 mmol\u002FL (transfusion and\u002For growth factor support is allowed)\n   * Absolute neutrophil count (ANC) ≥1500\u002Fmm3 or ≥1.5 × 109\u002FL\n   * Creatinine clearance (CrCl) ≥30 mL\u002Fmin as calculated using the Cockcroft-Gault equation or measured CrCl\n   * Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤3 × ULN (if liver metastases are present, ≤5 ×ULN)\n   * Total bilirubin (TBL) ≤1.5 × ULN if no liver metastases (\\\u003C3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases)\n   * Serum albumin ≥2.5 g\u002FdL or 25 g\u002FL\n   * Prothrombin time (PT) or Prothrombin time- international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)\u002Fpartial thromboplastin time (PTT) ≤1.5 × (ULN), except for subjects on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator\n10. Be willing to provide a qualifying tumor tissue specimen. A pretreatment tumor biopsy (if medically feasible) or otherwise archival tumor tissue is required. Samples must be of sufficient quantity and of adequate tumor tissue content (as defined in the Laboratory Manual).\n\n    1. A Baseline pretreatment tumor biopsy must be of the primary (if intact) and\u002For metastatic lesion(s) not previously irradiated and amenable to core biopsy. Any serious adverse event (SAE) directly related to the new biopsy should be reported as outlined in Section 8.\n    2. If not medically feasible to collect the pretreatment tumor biopsy, archival tumor tissue not previously irradiated must be collected from a biopsy on or after treatment with the most recent EGFR TKI cancer therapy regimen.\n11. If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at screening and must be willing to use a highly effective birth control upon enrollment, during the Treatment Period, and for 7 months, following the last dose of study drug. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose or confirmed by follicle stimulating hormone (FSH) test.\n12. Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.\n13. If male, the subject must be surgically sterile or willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 4 months following the last dose of study drug.\n14. Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and for at least 4 months after the final study drug administration.\n\nExclusion Criteria:\n\n1. Any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening.\n2. Clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:\n\n   1. any underlying pulmonary disorder (eg, pulmonary emboli, severe asthma, severe chronic obstructive lung disease (COPD), restrictive lung disease, pleural effusion);\n   2. any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis); OR prior pneumonectomy.\n3. Is receiving chronic systemic corticosteroids dosed at \\>10 mg prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Subjects who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study.\n4. Evidence of any leptomeningeal disease.\n5. Has clinically significant corneal disease.\n6. Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, active infection, psychiatric illness\u002Fsocial situations, geographical factors, substance abuse, or other factors which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.\n7. Evidence of clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the study. Subjects must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1.\n8. Inadequate washout period prior to Cycle 1 Day 1, defined as:\n\n   1. Whole brain radiation therapy \\\u003C14 days or stereotactic brain radiation therapy \\\u003C7 days.\n   2. Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)), \\\u003C14 days or 5 half-lives, whichever is longer.\n   3. Monoclonal antibodies other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFR) \\\u003C28 days.\n   4. Immune checkpoint inhibitor therapy \\\u003C 21 days.\n   5. Major surgery (excluding placement of vascular access) \\\u003C 28 days.\n   6. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation \\\u003C 28 days or palliative radiation therapy \\\u003C 14 days.\n   7. Chloroquine or hydroxychloroquine ≤ 14 days.\n9. Prior treatment with an HER3 antibody and\u002For antibody drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).\n10. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, grade ≤1 or baseline. Subjects with chronic Grade 2 toxicities may be enrolled at the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee.\n11. Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product.\n12. Has any primary malignancy other than locally advanced or metastatic NSCLC within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.\n13. Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1, including:\n\n    1. QT interval corrected by Fridericia's formula (QTcF) prolongation interval of \\>470 ms for females and \\>450 ms for males.\n    2. Left ventricular ejection fraction (LVEF) \\\u003C50% by either echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan.\n    3. Resting systolic blood pressure \\>180 mmHg or diastolic blood pressure \\>110 mmHg.\n    4. Myocardial infarction within 6 months.\n    5. New York Heart Association (NYHA) Classes 2 to 4 within 28 days.\n    6. Uncontrolled angina pectoris within 6 months.\n    7. Cardiac arrhythmia requiring antiarrhythmic treatment.\n14. Active Hepatitis B and\u002For Hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1.\n\n    a. Subjects with past or resolved Hepatitis B virus (HBV) infection are eligible if: i. Hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR ii. HBsAg positive and HBV DNA viral load is documented to be ≤ 2000 IU\u002FmL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases (in the absence of liver metastasis); OR iii. HBsAg positive and HBV DNA viral load is documented to be ≤ 2000 IU\u002FmL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal transaminases AST\u002FALT \\\u003C 3 ULN.\n\n    b. Subjects with a history of Hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection, is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but no less than 12 weeks, whichever is longer).\n15. Female subject who is pregnant or breastfeeding or intends to become pregnant during the study.\n16. Subjects with known human immunodeficiency virus (HIV) infection.\n17. Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's judgment, could affect the safety of the subject; alter the absorption, distribution, metabolism or excretion of the study drug; or confound the assessment of study results.\n18. Live virus vaccination 28 days prior to Cycle 1 Day 1.",{"count":268,"type":21},16,[52],"Activity of patritumab deruxtecan (U3-1402; HER3-DXd) has been shown in a phase I\u002FII study in patients with HER3 expressing breast cancer as well as in a phase I study in patients with EGFR TKI refractory EGFR mutation positive NSCLC with a preliminary ORR of 25%. HER3 expression can be seen in multiple tumor types and is therefore an attractive target for antibody drug conjugate (ADC) treatment. However, intra- and intertumor heterogeneity of HER3 expression might be substantial, as is seen for HER2, and might contribute to treatment failure or heterogeneous responses. In addition, HER3 expression is dynamic and has been shown to change over time.\n\nIn order to identify patients that may benefit most from treatment with patritumab deruxtecan, better knowledge of the in vivo behaviour of the drug is warranted. One way to visualize this behaviour is positron emission tomography (PET) imaging with radiolabelled antibodies (immune-PET). 89Zr-Patritumab deruxtecan PET\u002FCT can assess HER3 expression non-invasively at a whole body level, including sites that may be difficult to biopsy. It also visualizes and quantifies biodistribution of patritumab deruxtecan, thereby obtaining valuable information for safety and toxicity analyses.",[272,273,26],"Non-Small Cell Lung Carcinoma","Advanced Non-Small Cell Squamous Lung Cancer",[275],"At least one line of systemic treatment","2025-03-04",{"date":278,"type":31},"2025-03-06",{"date":280,"type":31},"2025-03-03",{"date":282,"type":21},"2028-05-01",{"name":284,"class":38},"The Netherlands Cancer Institute",{"id":286,"slug":287,"hasResults":11,"nctId":288,"briefTitle":289,"officialTitle":290,"acronym":4,"eligibilityCriteria":291,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":292,"targetDuration":4,"studyType":50,"phases":294,"briefSummary":295,"conditions":296,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":280,"lastUpdatePostDateStruct":298,"startDateStruct":299,"completionDateStruct":301,"leadSponsor":303,"locationsCount":306},"100565501","evaluating-high-dose-furmonertinib-with-bevacizumab-and-pemetrexed-for-egfrm-nsclc-with-leptomeningeal-metastasis-100565501","NCT06643000","Evaluating High-dose Furmonertinib with Bevacizumab and Pemetrexed for EGFRm NSCLC with Leptomeningeal Metastasis","A Single-center, Real-world Study Aimed At Evaluating the Efficacy and Safety of 240 Mg\u002Fd Furmonertinib Combined with Bevacizumab and Pemetrexed in the Treatment of Advanced NSCLC with EGFRm and Leptomeningeal Metastasis.","Inclusion Criteria:\n\n1. Have obtained written informed consent from the patient or his or her legal representative;\n2. The patient is ≥18 years old, male or female;\n3. Non-small cell lung cancer confirmed by histological or cytological pathology;\n4. Genetic testing confirming positive for classical or non-classical EGFR mutations;\n5. After comprehensive clinical evaluation according to the \"EANO-ESMO\" meningeal metastasis diagnostic criteria, the comprehensive clinical evaluation of patients with definite meningeal metastasis included symptom evaluation, imaging evaluation, and\u002For cerebrospinal fluid pathology evaluation;\n6. Patients with newly diagnosed leptomeningeal metastases and those with disease progression after previous antineoplastic therapy were eligible;\n7. ECOG Performance Status 0-3;\n8. Prior treatment with radiation or surgery targeting the central nervous system is permitted;\n9. Admit patients with CNS symptoms or signs, but those symptoms or signs are not life threatening;\n10. Fertile men or women with the possibility of becoming pregnant must use a highly effective method of contraception (such as oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicides) during the course of the trial and continue contraception for 12 months after the end of treatment.\n\nExclusion Criteria:\n\n* 1)Patients currently have tumors other than NSCLC; 2)Have had or have a history of other malignancies within the last 5 years, other than basal cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast that have been effectively controlled; 3)Serious digestive tract diseases that affect drug use and absorption, including but not limited to peptic ulcer, inflammatory bowel disease, etc.\n\n  4)Evidence of any severe or uncontrolled systemic disease, including uncontrolled hypertension, diabetes, and active bleeding, any that the investigator deems to be detrimental to the patient's participation in the study or to adherence to the protocol, or active infections including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV); 5)A history of interstitial lung disease, drug-induced interstitial lung disease, prior history of radiation pneumonia requiring steroid treatment, or any evidence of active interstitial lung disease; 6)The presence of significant arrhythmias (such as prolonged QT interval \\> 500ms) or heart failure (left ventricular ejection fraction \\\u003C 50%) 7)Pregnant or lactating women; 8)Patients who received a live vaccine within 4 weeks before treatment began; 9)Patients who are or have been involved in another clinical study within 4 weeks; 10)Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that, in the investigator's opinion, may increase the risks associated with participating in the study or may interfere with the interpretation of the study results; Or subjects who may not be able to complete the study or comply with the requirements of the study (for administrative or other reasons).",{"count":293,"type":21},60,[81],"The primary objective of this clinical study is to evaluate the efficacy of high-dose furmonertinib combined with bevacizumab and pemetrexed (triple therapy) in the treatment of non-small cell lung cancer (NSCLC) with leptomeningeal metastasis and epidermal growth factor receptor mutation (EGFRm) through overall survival (OS). The secondary objectives are to further assess the efficacy of the triple therapy in patients with EGFRm and leptomeningeal metastasis, including time to treatment failure (TTF), leptomeningeal objective response rate (ORR-LM), and clinical response rate.The study will also evaluate the impact of the triple therapy on quality of life using the EORTC QLQ-C30 scale and assess the safety of the therapy in EGFRm NSCLC patients with leptomeningeal metastasis, focusing primarily on adverse events and their severity (graded according to CTCAE v5.0), as well as their frequency.The exploratory objectives are to assess changes in intracranial pressure and the improvement rate of cerebrospinal fluid (CSF) before and after the triple therapy treatment. Additionally, the study will compare the genomic and epigenomic profile changes in circulating tumor DNA (ctDNA) from peripheral blood and cell-free DNA (cfDNA) from cerebrospinal fluid before and after treatment, and analyze their correlation with clinical outcomes, drug efficacy, and other clinical indicators.\n\nThe primary endpoint of this study is overall survival (OS). The secondary endpoints include time to treatment failure (TTF), leptomeningeal objective response rate (ORR-LM), clinical response rate, and quality of life assessment (EORTC QLQ-C30).The safety endpoints are adverse events and their severity (graded according to CTCAE v5.0), as well as the frequency of occurrence.\n\nA total of 60 patients are planned to be enrolled, targeting eligible advanced NSCLC patients with EGFR mutations and leptomeningeal metastasis.\n\nThe intervention consists of furmonertinib (240 mg\u002Fd, po) combined with bevacizumab (15 mg\u002Fkg, every 3 weeks, ivgtt) and pemetrexed (50 mg) intrathecal chemotherapy \u002F pemetrexed (500 mg\u002Fm²) intravenous chemotherapy, administered every 3 weeks.",[84,297,26],"Leptomeningeal Metastasis",{"date":278,"type":31},{"date":300,"type":31},"2024-12-20",{"date":302,"type":21},"2025-05-30",{"name":304,"class":305},"Henan Cancer Hospital","OTHER_GOV",2,{"id":308,"slug":309,"hasResults":11,"nctId":310,"briefTitle":311,"officialTitle":312,"acronym":4,"eligibilityCriteria":313,"healthyVolunteers":11,"sex":17,"minAge":314,"maxAge":315,"enrollmentInfo":316,"targetDuration":4,"studyType":50,"phases":317,"briefSummary":318,"conditions":319,"keywords":321,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":325,"lastUpdatePostDateStruct":326,"startDateStruct":328,"completionDateStruct":330,"leadSponsor":332,"locationsCount":69},"100521547","phase-1-nintedanib-plus-egfr-tki-in-egfr-mutated-non-small-cell-lung-cancer-patients-100521547","NCT06071013","Nintedanib Plus EGFR TKI In EGFR-mutated Non-small Cell Lung Cancer Patients","A Phase I\u002FPhase II Study of Nintedanib Plus EGFR TKI In EGFR-mutated Non-small Cell Lung Cancer Patients","Inclusion Criteria:\n\n1. Participants between 20 to 70 years old, are pathologically confirmed advanced (stage III and IV) non-small cell lung cancer.\n2. Positive EGFR mutations are diagenesis.\n3. Participants with histologically\u002Fcytologically confirmed locally advanced or metastatic adenocarcinoma subtype NSCLC after the failure of first-line EGFR tyrosine kinase inhibitors- gefitinib, erlotinib, afatinib, or osimertinib.\n4. Participants must have adequate hepatic, renal, and bone marrow function\n\nExclusion Criteria:\n\n1. Participants previously received first-line EGFR tyrosine kinase inhibitor with serious side effects.\n2. Participants have known hypertension, and chronic liver and gastrointestinal disease.\n3. Participants have known brain metastasis.\n4. Female participants who are pregnant or breast-feeding\n5. Participants have a known diagnosis of negative nPKCδ expression by immunohistochemistry (IHC).","20 Years","70 Years",{"count":109,"type":21},[111,52],"The purpose of this study is to evaluate the efficacy and safety of Nintedanib with EGFR-TKI in participants with advanced EGFR-TKI-resistant non-small cell lung cancer",[84,26,320],"EGFR-TKI Resistant Mutation",[322,323,324],"nPKC delta","Angiogenesis","EGFR TKI drug resistant","2025-01-20",{"date":327,"type":31},"2025-01-23",{"date":329,"type":31},"2024-02-23",{"date":331,"type":21},"2026-08-27",{"name":333,"class":38},"China Medical University Hospital",{"id":335,"slug":336,"hasResults":11,"nctId":337,"briefTitle":338,"officialTitle":339,"acronym":340,"eligibilityCriteria":341,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":342,"targetDuration":344,"studyType":22,"phases":4,"briefSummary":345,"conditions":346,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":350,"lastUpdatePostDateStruct":351,"startDateStruct":353,"completionDateStruct":355,"leadSponsor":357,"locationsCount":69},"100485242","exploring-the-mechanism-of-primary-resistance-to-third-generation-egfr-tkis-as-first-line-treatment-in-egfr-positive-advanced-nsclc-precise-study-100485242","NCT05598528","Exploring the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)","A Multicenter Clinical Study to Explore the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)","PRECISE","Inclusion Criteria:\n\n1. Age \\>18 years;\n2. Histological or cytopathological diagnosed NSCLC;\n3. According to the American Joint Committee on Cancer (AJCC) eighth edition of the Lung Cancer Staging Manual, the clinical stage is unresectable IIIB-IV or recurrence and metastasis after surgery;\n4. At least one measurable lesion can be evaluated according to the Response Evaluation Criteria In Solid Tumours v1.1 (RECIST1.1) criteria;\n5. Positive EGFR mutation confirmed by tissue or cytology (pleural fluid, cerebrospinal fluid, etc.);\n6. Use of third-generation EGFR-TKIs approved by the NMPA for NSCLC as first-line therapy;\n7. Cooperate with the provision of clinicopathological data, imaging data, sample collection, and follow-up required for the research process, and agree to use the test data for subsequent research and product development;\n8. Agree to participate in this study and sign an informed consent form.\n\nExclusion Criteria:\n\n1. Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form;\n2. Pregnant and lactating women;\n3. Other malignant neoplastic diseases within 3 years;\n4. Patients who have undergone other clinical drug trials;\n5. Received systemic anti-tumor therapy within 2 years;",{"count":343,"type":21},210,"5 Years","Lung cancer is currently the world's largest malignant tumor for cancer-related deaths with non-small cell lung cancer (NSCLC) accounting for 80%-85%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), especially the 3rd-generation EGFR-TKIs have demonstrated strong antitumor effects in EGFR-positive patients.\n\nHowever, approximately 20% of EGFR-positive were primarily resistant to 3rd generation EGFR-TKIs, i.e., clinical non-response or disease progression in the short term.\n\nThis study aimed to clarify the molecular indicators that predict the benefits of 3-rd EGFR-TKIs as first-line therapy in NSCLCpatients with EGFR-positive. Further, to clarify their primary drug resistance mechanisms, which is of great significance for the treatment and clinical decision-making of NSCLC disease.",[347,26,320,348,349],"Lung Cancer, Non-small Cell","Primary Resistance","Circulating Tumor DNA","2024-11-27",{"date":352,"type":31},"2024-12-02",{"date":354,"type":31},"2021-09-28",{"date":356,"type":21},"2026-12-31",{"name":358,"class":38},"Second Xiangya Hospital of Central South University",{"id":360,"slug":361,"hasResults":11,"nctId":362,"briefTitle":363,"officialTitle":364,"acronym":365,"eligibilityCriteria":366,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":367,"targetDuration":4,"studyType":50,"phases":369,"briefSummary":370,"conditions":371,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":375,"lastUpdatePostDateStruct":376,"startDateStruct":378,"completionDateStruct":380,"leadSponsor":382,"locationsCount":69},"100387296","phase-2-treatment-strategies-and-survival-outcome-for-non-small-cell-lung-cancer-with-oncogenic-mutation-100387296","NCT04322890","Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation","Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation.","PIKACHU","Inclusion Criteria:\n\n1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.\n2. Age ≥ 18 years.\n3. Histologically or cytologically confirmed, Stage IV NSCLC.\n4. Oncogenic mutations confirmed by an accredited local laboratory, including EGFR, ALK, ROS1 etc.\n5. ECOG 0-1.\n6. Predicted survival ≥ 12 weeks.\n7. Adequate bone marrow hematopoiesis and organ function\n8. Presence of measurable lesions according to RECIST 1.1.\n\nExclusion Criteria:\n\nThe patient did not match from the Inclusion Criteria.",{"count":368,"type":21},6000,[52],"The purpose of this study is to assess the Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation.",[372,26,173,373,374],"Non Small Cell Lung Cancer","ROS1 Gene Mutation","MET Gene Mutation","2024-10-19",{"date":377,"type":31},"2024-10-22",{"date":379,"type":31},"2020-04-16",{"date":381,"type":21},"2027-12-24",{"name":383,"class":38},"Hunan Province Tumor Hospital",{"id":385,"slug":386,"hasResults":11,"nctId":387,"briefTitle":388,"officialTitle":389,"acronym":4,"eligibilityCriteria":390,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":391,"targetDuration":4,"studyType":50,"phases":393,"briefSummary":394,"conditions":395,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":397,"lastUpdatePostDateStruct":398,"startDateStruct":400,"completionDateStruct":402,"leadSponsor":403,"locationsCount":69},"100369053","phase-1-alisertib-in-combination-with-osimertinib-in-metastatic-egfr-mutant-lung-cancer-100369053","NCT04085315","Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer","A Phase I\u002FIb Study of Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer","Inclusion Criteria:\n\n1. Patients must have histologically confirmed stage IV non-small cell lung cancer.\n2. Male or female patients \\>=18 years of age\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n4. Documented activating EGFR mutation (Exon 19 deletion, Exon 19 insertion, E709K, G719X, S768I, V769L, T790M, L833F, L833V, V834L, H835L, L858R, A859S, K860I, L861Q, A871E, V843I, or H870R) on tumor sample or cell-free DNA sample performed in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory.\n5. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.\n6. Clinical laboratory values as specified below within 7 days before the first dose of study drug (if applicable):\n\n   1. Absolute neutrophil count (ANC) \\> 1500\u002Fmm\\^3\n   2. Absolute lymphocyte count \\> 500 mm\\^3\n   3. Platelets \\> 100,000\u002Fmm\\^3\n   4. Hemoglobin (Hgb) \\> 9 g\u002FdL. Values must be obtained without need for red blood cell transfusion support within 14 days. However, erythrocyte growth factor is allowed as per published American Society of Clinical Oncology (ASCO) guidelines.\n   5. Total bilirubin ≤ 1.5 x upper limit of normal (ULN). Patients with Gilbert's syndrome may be allowed on study if total bilirubin is \\\u003C= 3 x upper limit of normal (ULN) if direct bilirubin is \\\u003C= 1.5 x upper limit of normal (ULN).\n   6. Serum glutamic-oxaloacetic transaminase (SGOT) \u002F aspartate aminotransferase (AST) and serum glutamic-pyruvic transaminase (SGPT) \u002F alanine aminotransferase (ALT) \\\u003C 2.5 x ULN. AST and\u002For ALT may be up to 5 x ULN if with known liver metastases.\n   7. Renal function as defined by calculated creatinine clearance \\>=30 ml\u002Fmin (Cockcroft-Gault Formula).\n7. Willing to provide blood and tissue for correlative research purposes.\n8. Willing to undergo pre-treatment research biopsy, OR donate archived tissue from a biopsy performed within 60 days of the first dose of study drug is available.\n9. Female patients who:\n\n   1. Are postmenopausal (see Appendix 6) for at least 1 year before the screening visit, OR\n   2. Are surgically sterile, OR\n   3. If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time (see Appendix 6), from the time of signing the informed consent through 180 days after the last dose of study drug, OR\n   4. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \\[e.g., calendar, ovulation, symptothermal, post-ovulation methods\\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)\n10. Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:\n\n    1. Agree to practice effective barrier contraception during the entire study treatment period and through 120 after the last dose of study drug, OR\n    2. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \\[e.g., calendar, ovulation, symptothermal, post-ovulation methods\\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)\n11. Voluntary written consent must be given before performance of any study-related procedure not part of standard of care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.\n12. Currently receiving and tolerating osimertinib 80 mg PO daily with no current grade 2 or greater AE attributable to osimertinib.\n13. Evidence of disease progression on imaging (computerized tomography (CT) scan, magnetic resonance imaging (MRI), or Positron Emission Tomography (PET) CT within the last 30 days.\n14. Resolution of all acute toxic effects of prior chemotherapy, immunotherapy, radiotherapy or surgical procedures to less than or equal to grade 2 per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.\n\n    Inclusion Criteria (Cohort A): Must meet inclusion criteria below in addition to 1-14 above:\n15. Patients must have received no more than one additional line of systemic therapy to treat lung cancer other than osimertinib (re-treatment with osimertinib after other systemic lung cancer therapy will not count as a line of therapy). A line of therapy equals at least one month of treatment with discontinuation of therapy due to disease progression or intolerability. Patients who have received adjuvant or neoadjuvant osimertinib, chemotherapy, or immunotherapy for surgically resectable NSCLC, or chemotherapy + radiation +\u002F- immunotherapy for locally advanced NSCLC, will not be considered a line of therapy if it is equal to or greater than 12 months since completing their treatment.\n16. Patients must be currently receiving osimertinib 80 mg for the treatment of metastatic disease or have evidence of metastatic disease recurrence while receiving adjuvant osimertinib therapy.\n\n    Inclusion Criteria (Cohort B): Must meet inclusion criteria below in addition to 1-7, 9-12, and 14. Inclusion criteria 8 and 13 are not required. The following inclusion criteria must also be met:\n17. Currently receiving osimertinib 80 mg as 1st line therapy for metastatic NSCLC. Patients who have received adjuvant or neoadjuvant, chemotherapy, or immunotherapy for surgically resectable NSCLC, or chemotherapy + radiation +\u002F- immunotherapy for locally advanced NSCLC, will be allowed if it is equal to or greater than 12 months since completing their treatment.\n18. Meet RECIST 1.1 criteria for PR or SD to osimertinib, including a confirmation scan.\n19. Have received osimertinib 80 mg for a minimum of 90 days, but no more than 180 days.\n\n    Inclusion Criteria (Cohort C): Must meet inclusion criteria 1-7 and 9-16 above. The following inclusion criterion must also be met:\n20. Willing to undergo pre-treatment research biopsy, if deemed safe by the investigator, or willing to donate archived tissue from a biopsy performed within 60 days prior to the first dose of study drug. Note: Pre-treatment tissue is mandatory for Cohort C and will be used for a CLIA-approved TP53 mutation test during screening. To be eligible for Cohort C, patients must not have a known TP53 missense mutation, nonsense mutation, frameshift mutation, in frame deletion, or whole gene deletion (see also exclusion criterion #22).\n\nExclusion Criteria\n\n1. Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.\n2. Prior allogeneic bone marrow or organ transplantation\n3. Known Gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib. Examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease\n4. Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to alisertib.\n5. Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.\n6. Requirement for constant administration of proton pump inhibitor, Histamine 2 (H2) antagonist, or pancreatic enzymes throughout the study. The intermittent use of H2-antagonists and antacids (including carafate) is only allowed within these guidelines:\n\n   1. H2 antagonists until Day -1 and after the dosing of alisertib is done\n   2. Antacid formulations until 2 hours before dosing and after 2 hours following dosing.\n   3. Proton Pump Inhibitor (PPI) is allowed until Day -5 of first alisertib dose. PPIs are prohibited throughout the study.\n7. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant.\n8. QT interval corrected (QTc) using Fridericia's method (QTCF) \\> 470 milliseconds (msec). The following formula can be used to calculate QTcF for subjects with a wide QRS complex caused by the bundle branch block, QTcF = measured QTcF - (QRS - 100msec).\n9. Female subject who is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.\n10. Female patient who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).\n11. Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).\n12. Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.\n13. Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer or breast cancer, or thyroid cancer after curative therapy\n14. Patients who are currently receiving treatment with contraindicated QTcF prolonging medications or potent CYP3A4 inducers\u002Finhibitors if that treatment cannot be either discontinued or switched to a different medication prior to first day of study treatment.\n15. Patients with central nervous system (CNS) metastases who are neurologically unstable (as defined by need for steroids in last 14 days).\n16. Known leptomeningeal carcinomatosis.\n\n    Exclusion Criteria (Cohort A): Must meet exclusion criteria 1-16 above. The following exclusion criteria must also be met:\n17. Known small cell lung cancer transformation on osimertinib resistance biopsy.\n18. Known EGFR C797S osimertinib resistance mutation, hepatocyte growth factor receptor (MET) amplification, oncogenic fusion involving neurotrophic tyrosine receptor kinase (NTRK), RET, ALK, ROS-1, or BRAF, BRAF V600E, or oncogenic KRAS mutation determined by Clinical Laboratory Improvement Amendments (CLIA)-approved test on osimertinib resistance biopsy or cell-free deoxyribonucleic acid (DNA) test performed at osimertinib resistance.\n\n    Exclusion Criteria (Cohort B): Must meet exclusion criteria 1-16 above. The following exclusion criteria must also be met:\n19. Evidence of complete response (CR) or progressive disease (PD) to osimertinib by RECIST 1.1 criteria on imaging within 30 days prior to starting alisertib.\n20. Prior treatment with adjuvant osimertinib.\n21. Prior treatment with an EGFR TKI other than osimertinib.\n\n    Exclusion Criteria (Cohort C): Must not meet exclusion criteria 1-18 above. The following exclusion criterion must also not be met:\n22. Known TP53 missense mutation, nonsense mutation, frameshift mutation, in frame deletion, or whole gene deletion determined by CLIA-approved test on any prior patient lung cancer biopsy.",{"count":392,"type":21},38,[111],"This phase I\u002FIb trial studies the side effects and best dose of alisertib when given together with osimertinib in treating patients with EGFR-mutated stage IV lung cancer. Alisertib may stop the growth of tumor cells by blocking a specific protein (Aurora Kinase A) that researchers believe may be important for the growth of lung cancer. Osimertinib may reduce tumor growth by blocking the action of a certain mutant protein (EGFR). This study may help researchers test the safety of alisertib at different dose levels in combination with osimertinib, and to find out what effects, good and\u002For bad, it has on EGFR-mutated lung cancer.",[396,26],"Lung Cancer Metastatic","2024-06-06",{"date":399,"type":31},"2024-06-10",{"date":401,"type":31},"2019-11-12",{"date":356,"type":21},{"name":404,"class":38},"Collin Blakely",{"id":406,"slug":407,"hasResults":11,"nctId":408,"briefTitle":409,"officialTitle":410,"acronym":4,"eligibilityCriteria":411,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":194,"enrollmentInfo":412,"targetDuration":4,"studyType":50,"phases":414,"briefSummary":415,"conditions":416,"keywords":419,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":421,"lastUpdatePostDateStruct":422,"startDateStruct":424,"completionDateStruct":426,"leadSponsor":428,"locationsCount":4},"100549601","phase-2-osimertinib-and-etoposide-as-first-line-treatment-in-osimertinib-resistant-advanced-egfr-mutant-nsclc-100549601","NCT06436144","Osimertinib and Etoposide as First-Line Treatment in Osimertinib-Resistant Advanced EGFR-Mutant NSCLC","A Single-Center, Prospective, Single-Arm, Observational Study Evaluating the Efficacy and Safety of Osimertinib Combined With Etoposide as First-Line Treatment in Patients With Osimertinib-Resistant or -Insensitive, Advanced EGFR-Mutant Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n1. Age 18 to 79 years.\n2. Locally advanced (stage IIIB) or metastatic (stage IV) EGFR-mutant NSCLC.\n3. Harboring an EGFR sensitizing mutation (Exon 19 deletion or L858R).\n4. Received at least two cycles of first-line osimertinib treatment, with a best response of stable disease or slow progression.\n5. Life expectancy greater than 3 months.\n6. At least one measurable tumor lesion meeting the following criteria:\n\n1.No prior radiation therapy; 2.Measurable by chest CT or PET-CT, with a longest diameter ≥ 10 mm at baseline (short axis ≥ 15 mm for lymph nodes); 3.Amenable to accurate repeated measurements.\n\nExclusion Criteria:\n\n1. Currently receiving or planning to receive other anti-cancer therapies.\n2. Having contraindications to osimertinib or etoposide.\n3. Harboring known targetable osimertinib resistance mechanisms.",{"count":413,"type":21},93,[52],"Osimertinib, though a standard first-line treatment for EGFR-mutant advanced NSCLC, shows primary resistance in 10-30% of patients, leading to disease progression within 3-4 months. This resistance is linked to co-mutations in genes like TP53, RB1, and PIK3CA, among others. Studies indicate that Topo II inhibitor Etoposide (VP-16) can reduce cell survival, enhance DNA damage, and delay resistance in Osimertinib-resistant cells, suggesting a potential combination therapy to manage resistance.This study is a single-center, prospective, single-arm study evaluating the efficacy and safety of osimertinib combined with etoposide as a first-line treatment in patients with osimertinib-resistant or -insensitive advanced non-small cell lung cancer (NSCLC). The study focuses on patients with advanced NSCLC (stage IIIB or IV) with EGFR-sensitive mutations who developed slow resistance to osimertinib and for whom secondary biopsy after resistance did not identify any therapeutic targets.",[372,26,417,418],"Non Small Cell Lung Cancer Stage IIIB","Non-small Cell Lung Cancer Stage IV",[372,26,420],"Primary drug resistance of oxitinib","2024-05-28",{"date":423,"type":31},"2024-05-30",{"date":425,"type":21},"2024-06",{"date":427,"type":21},"2029-12",{"name":429,"class":38},"Daping Hospital and the Research Institute of Surgery of the Third Military Medical University",{"id":431,"slug":432,"hasResults":11,"nctId":433,"briefTitle":434,"officialTitle":435,"acronym":4,"eligibilityCriteria":436,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":437,"targetDuration":4,"studyType":50,"phases":439,"briefSummary":441,"conditions":442,"keywords":4,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":444,"lastUpdatePostDateStruct":445,"startDateStruct":447,"completionDateStruct":449,"leadSponsor":451,"locationsCount":4},"100540922","phase-3-adjuvant-target-therapy-guided-by-ctdna-mrd-in-patients-with-egfr-mutant-ii-iiia-non-small-cell-lung-cancer-ectop-1022-100540922","NCT06323148","Adjuvant Target Therapy Guided by ctDNA-MRD in Patients With EGFR-mutant II-IIIA Non-small Cell Lung Cancer (ECTOP-1022)","Adjuvant Target Therapy Guided by ctDNA-MRD in Patients With EGFR-mutant II-IIIA","Inclusion Criteria:\n\n1. Age greater than 18 years old, both males and females are eligible.\n2. Histologically confirmed diagnosis of non-small cell lung cancer.\n3. Diagnosis of stage II-IIIA (N1-N2) non-small cell lung cancer based on the 8th edition TNM staging guidelines combined with radiological evaluation.\n4. EGFR mutation-positive status confirmed through molecular testing (such as ARMS-PCR or high-throughput sequencing), specifically with mutations 19del or 21L858R.\n5. Able to undergo R0 surgical resection.\n6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-1. Expected survival of more than 12 months.\n7. Baseline blood routine and biochemical indicators meeting the following criteria:\n\n   * Absolute neutrophil count (ANC) ≥ 1.5 × 10\\^9\u002FL;\n   * Lymphocyte count ≥ 0.5 × 10\\^9\u002FL;\n   * Platelet count ≥ 100 × 10\\^9\u002FL;\n   * Hemoglobin ≥ 9 g\u002FdL.\n   * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);\n   * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 times ULN.\n8. Patients must provide informed consent, either directly or through their legally authorized representatives, after being informed about the study.\n\nExclusion Criteria:\n\n1. Pathological diagnosis of mixed-type lung cancer (including a history of small cell lung cancer or non-adenocarcinoma).\n2. Received anti-tumor therapy before surgery (including radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.).\n3. Rx, R1, R2 surgical resection.\n4. Received blood transfusion during surgery or within 2 weeks before surgery.\n5. Pregnant or lactating female patients.\n6. History of other malignant tumors within the past 5 years, except for cases where other malignant tumors have been cured solely through surgery with a disease-free interval of at least 10 years, curable basal cell carcinoma of the skin, and cervical carcinoma in situ.\n7. Any unstable systemic diseases (including active infections, uncontrolled hypertension, unstable angina pectoris, congestive heart failure, myocardial infarction within the past year, severe arrhythmias requiring medication, liver, kidney, or metabolic diseases).\n8. Evidence of any other diseases, neurological or metabolic functional disorders, physical examination findings, or laboratory findings that would place the subject at high risk of treatment-related complications.\n9. Other factors deemed by the investigators to potentially affect the study process.",{"count":438,"type":21},226,[440],"PHASE3","This study plans to conduct ctDNA testing on EGFR mutation-positive stage II-IIIA (N1-N2) NSCLC patients after radical surgery (R0 resection). Patients with positive ctDNA testing will receive standard treatment according to clinical guidelines, while patients with negative ctDNA testing will be assessed based on comprehensive clinical and pathological characteristics. After receiving or not receiving standard adjuvant chemotherapy, patients will be randomly assigned in a 1:1 ratio to either the observation follow-up group (experimental group) or the osimertinib adjuvant treatment group (control group). The aim is to explore whether observation follow-up for patients with negative ctDNA after surgery has a prognosis non-inferior to osimertinib treatment, and to investigate the disease-free survival rate of EGFR mutation-positive stage II-IIIA (N1-N2) NSCLC patients with positive ctDNA after surgery receiving osimertinib adjuvant treatment, providing more precise treatment guidance for adjuvant therapy in this specific type of NSCLC patients with EGFR mutation-positive tumors.",[200,26,443],"Minimal Residual Disease","2024-03-14",{"date":446,"type":31},"2024-03-21",{"date":448,"type":21},"2024-04-01",{"date":450,"type":21},"2029-03-31",{"name":452,"class":38},"Fudan University",{"id":454,"slug":455,"hasResults":11,"nctId":456,"briefTitle":457,"officialTitle":458,"acronym":4,"eligibilityCriteria":459,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":460,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":461,"conditions":462,"keywords":464,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":467,"lastUpdatePostDateStruct":468,"startDateStruct":470,"completionDateStruct":472,"leadSponsor":474,"locationsCount":4},"100525123","the-efficacy-of-double-dose-furmonertinib-in-the-treatment-of-patients-with-slow-osimertinib-resistant-nsclc-100525123","NCT06117644","The Efficacy of Double-dose Furmonertinib in the Treatment of Patients With Slow Osimertinib-resistant NSCLC","A Single-center, Prospective Study of the Efficacy of Double-dose Furmonertinib in the Treatment of Patients With Slow Osimertinib-resistant Non-small Cell Lung Cancer","Inclusion Criteria:\n\n1. Age ≥ 18 years old;\n2. EGFRm NSCLC of local progression (IIIB stage) or metastasis (IV stage);\n3. previously confirmed to have EGFR (Ex19del or L858R) mutation, or T790M, received Osimertinib treatment. According to Recist 1.1 imaging findings, the focus progressed slowly and there was no systemic explosive progress (definition of slow progress: disease control \\> 6 months, slightly increased tumor load and symptom score ≤ 1);\n4. patients who intend to use Furmonertinib (double dose, 160mg) anticancer therapy;\n5. At least one tumor lesion in the patient can meet the following requirements: it has not been irradiated in the past and can be accurately measured, the longest diameter of the baseline phase is ≥ 10mm (in the case of lymph nodes, short axis ≥ 15mm is required), and the measurement method can be chest CT or PET-CT, as long as repeated measurements can be completed accurately;\n6. No treatable target was found in the second biopsy after drug resistance;\n7. The survival time was more than 3 months;\n\nExclusion Criteria:\n\n1. Patients who have been treated with Furmonertinib;\n2. Patients who intend to use anticancer therapy other than Furmonertinib recently;\n3. Contraindications for the use of Furmonertinib;",{"count":20,"type":21},"This study is a single-center, prospective, single-arm study of the efficacy of double-dose Furmonertinib in the treatment of patients with slow Osimertinib-resistant non-small cell lung cancer, mainly in patients with advanced non-small cell lung cancer with EGFR-sensitive mutations in stage IIIB or IV, slow drug resistance after treatment with Osimertinib, and no therapeutic target was found by secondary biopsy after drug resistance.",[372,26,463,418],"Non Small Cell Lung Cancer Stage IIIA",[372,26,465,466],"Furmonertinib","Drug Resistance","2023-10-31",{"date":469,"type":31},"2023-11-07",{"date":471,"type":21},"2023-11-01",{"date":473,"type":21},"2026-10-01",{"name":429,"class":38},{"id":476,"slug":477,"hasResults":11,"nctId":478,"briefTitle":479,"officialTitle":480,"acronym":4,"eligibilityCriteria":481,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":482,"targetDuration":4,"studyType":50,"phases":484,"briefSummary":485,"conditions":486,"keywords":487,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":491,"lastUpdatePostDateStruct":492,"startDateStruct":494,"completionDateStruct":496,"leadSponsor":497,"locationsCount":4},"100517526","phase-2-osimertinib-combined-with-aspirin-neoadjuvant-therapy-for-resectable-egfr-mutated-nsclc-patients-100517526","NCT06018688","Osimertinib Combined With Aspirin Neoadjuvant Therapy for Resectable EGFR Mutated NSCLC Patients.","A Phase II Study Evaluating Osimertinib Combined With Aspirin Neoadjuvant Therapy for Resectable EGFR Mutated Non-small Cell Lung Cancer (NSCLC)","Inclusion Criteria:\n\n1. Patients with resectable stage IIA-IIIA lung adenocarcinoma.\n2. Patients with EGFR sensitizing mutations (Ex19del or L858R).\n3. Intended neoadjuvant therapy with osimertinib, with an anticipated survival expectancy of more than 3 months.\n4. ECOG PS 0\u002F1.\n5. Primary lesion diameter of at least 1 cm.\n6. Patients who have previously taken or are currently taking aspirin therapy are allowed.\n\nExclusion Criteria:\n\n1. Currently receiving other anticoagulant therapy.\n2. Previously treated with systemic therapy for NSCLC.\n3. Other positive driver mutations, including ALK, ROS1, MET14 exon skipping, BRAF, RET, etc.\n4. Contraindications to the use of osimertinib and aspirin.",{"count":483,"type":21},44,[52],"This is a single-center, prospective, single-arm, phase II study of Osimertinib combined with Aspirin neoadjuvant therapy for resectable, EGFR mutated non-small cell lung cancer (NSCLC). It is mainly aimed at the population of patients with primary IIA- IIIA EGFR sensitive mutations that are intended to be treated with Osimertinib neoadjuvant therapy.",[372,26],[141,488,489,59,490],"Aspirin","Osimertinib","neoadjuvant therapy","2023-09-16",{"date":493,"type":31},"2023-09-21",{"date":495,"type":21},"2023-09-15",{"date":33,"type":21},{"name":429,"class":38},{"id":499,"slug":500,"hasResults":11,"nctId":501,"briefTitle":502,"officialTitle":502,"acronym":4,"eligibilityCriteria":503,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":504,"targetDuration":4,"studyType":50,"phases":506,"briefSummary":507,"conditions":508,"keywords":510,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":513,"lastUpdatePostDateStruct":514,"startDateStruct":516,"completionDateStruct":518,"leadSponsor":520,"locationsCount":69},"100492908","a-pilot-study-to-understand-the-impact-of-therapy-with-tumour-treating-fields-ttfields-in-nsclc-100492908","NCT05698264","A Pilot Study to Understand the Impact of Therapy With Tumour Treating Fields (TTFields) in NSCLC","Inclusion Criteria:\n\n1. Male and female patients 18 years of age and older.\n2. Have histologically or cytologically confirmed lung cancer.\n3. Documented next generation sequencing assay performed on tumor sample in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory.\n4. Have at least 1 measurable lesion per RECIST v1.1\n5. Have life expectancy ≥3 months.\n6. Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.\n7. Must provide a signed and dated informed consent indicating that the participants have been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.\n8. Have the willingness and ability to comply with scheduled visits and study procedures.\n9. Cohort A, confirmed EGFR mutation.\n\nExclusion Criteria:\n\n1. Implanted electronic devices (e.g. pacemaker) in the upper torso.\n2. Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ or prostate cancer, which are allowed within 3 years).\n3. Have any condition or illness that, in the opinion of the investigator, would compromise participants' safety or interfere with the evaluation.\n4. Be pregnant or breastfeeding.",{"count":505,"type":21},50,[81],"Low intensity, intermediate frequency (100-300 kHz) alternating electric fields, also known as Tumor Treating Fields (TTFields) were found to have a profound inhibitory effect on the growth rate of a variety of human cancer cells. Previous study showed anti-tumor activity in respect of melanoma, glioblastoma (GBM), breast carcinoma and NSCLC cell lines. This study aims to assess the impact of TTFields on NSCLC though the understanding of tumor evolution and peripheral lymphocytes activity and proliferation.\n\nConcomitant to drug therapy, patients will receive treatment with Tumor Treating Fields (TTFields), generated by the medical device NovoTTF-200T with a recommended duration of minimum 18 h a day. TTFields administered using insulated transducer arrays applied to the skin surrounding the region of a malignant tumor.\n\n50 patients will be recruited according to the study design in two cohorts and will receive TTFields therapy: Cohort A: Adult NSCLC EGFR positive mutation. Cohort B: Adult NSCLC patients to be treated with PD-1 inhibitors. The cohort A will focus on the clonal evolution in EGFR mutated lung cancer patients by using circulating tumor DNA (ctDNA) analysis of paired baseline and end-of-treatment (EOT) plasma samples. The cohort B will study the impact of TTField on the profile, activity, and proliferation of peripheral lymphocytes. Lymphocytes will be purified from whole blood samples for the profile, proliferation, and activity analyzed by FACS.\n\nTreatment with TTFields will be administered until progressive disease, unacceptable toxicity1, withdrawal of consent or death. After the end of treatment, the patients will be followed until data cutoff date or 2 years after the last patient had entered the study.",[372,26,509],"Immune Checkpoint Inhibitor",[511,512,372,57,26],"TTFields","immune checkpoint inhibitor","2023-01-22",{"date":515,"type":31},"2023-01-26",{"date":517,"type":21},"2023-01-20",{"date":519,"type":21},"2028-12-31",{"name":521,"class":38},"Nir Peled",{"id":523,"slug":524,"hasResults":11,"nctId":525,"briefTitle":526,"officialTitle":527,"acronym":4,"eligibilityCriteria":528,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":529,"targetDuration":4,"studyType":50,"phases":531,"briefSummary":532,"conditions":533,"keywords":536,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":538,"lastUpdatePostDateStruct":539,"startDateStruct":541,"completionDateStruct":543,"leadSponsor":544,"locationsCount":69},"100477953","phase-2-neoadjuvant-furmonertinib-plus-bevacizumab-or-furmonertinib-monotherapy-for-resectable-and-potentially-resectable-stage-iii-iva-egfr-mutation-positive-lung-adenocarcinoma-100477953","NCT05503667","Neoadjuvant Furmonertinib Plus Bevacizumab or Furmonertinib Monotherapy for Resectable and Potentially Resectable Stage III-IVA EGFR Mutation-Positive Lung Adenocarcinoma","Neoadjuvant Furmonertinib Plus Bevacizumab or Furmonertinib Monotherapy for Resectable and Potentially Resectable Stage III-IVA EGFR Mutation-Positive Lung Adenocarcinoma: A Randomized, Controlled, Open-label, Single-center Phase II Clinical Trial","Inclusion Criteria:\n\n* Lung adenocarcinoma patient with EGFR sensitive mutation as confirmed by needle biopsy;\n* At stage III-IVA (TNM Staging, Version 8) as identified by chest CT, PET-CT or\u002Fand EBUS;\n* No systemic metastasis (confirmed by head MRI, whole body bone scan, PET-CT, liver and adrenal CT, etc.);\n* With the feasiblility or potential feasibility to receive radical surgery (radical lung lobectomy+systematic lymph node dissection);\n* Good lung function that could tolerate surgical treatment;\n* Aged \\>= 18 years;\n* At least one measurable tumor foci (the longest diameter measured by CT shall be \\> 10 mm);\n* Other major organs shall function well (liver, kidney, blood system, etc.):\n* ECOG PS score shall be 0-1;\n* The child-bearing female must undergo pregnancy test within 7 days before starting the treatment and the result shall be negative. Reliable contraceptive measures, such as intrauterine device, contraceptive pill and condom, shall be adopted during the trial and within 30 days after completion of the trial. The child-bearing male shall use condom for contraception during the trial and within 30 days after completion of the trial;\n* The patient shall sign the Informed Consent Form.\n\nExclusion Criteria:\n\n* The patient has undergone any systemic anti-cancer treatment for NSCLC, including cytotoxic drug treatment, targeted drug treatment and experimental treatment, etc.;\n* The patient suffers from any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina pectoris, angina pectoris that starts to attack within the last 3 months, congestive heart failure \\[≥ Grade II specified by New York Heart Association (NYHA)\\], cardiac infarction (6 months before enrollment), severe arrhythmia and liver, kidney or metabolic diseases that requires drug treatment;\n* The patient is a carrier of HIV;\n* The patient is currently suffering from interstitial lung disease;\n* The patient had undergone other major systemic operations or suffered from severe trauma within 3 months before the trial;\n* The patient is allergic to furmonertinib or its any excipients;\n* The patient is allergic to bevacizumab or its any excipients;\n* The female patient is in pregnancy or lactation period;\n* There are any conditions under which the investigator considers the patient is not suitable to be enrolled.",{"count":530,"type":21},96,[52],"To explore the efficacy and safety of neoadjuvant furmonertinib combined with bevacizumab in the treatment of resectable and potentially resectable stage III-IVA EGFR mutation-positive lung adenocarcinoma.",[534,535,26],"Lung Adenocarcinoma Stage III","Lung Adenocarcinoma Stage IV",[537],"neoadjuvant chemoimmunotherapy","2022-08-13",{"date":540,"type":31},"2022-08-17",{"date":542,"type":31},"2022-02-01",{"date":519,"type":21},{"name":545,"class":38},"Shanghai Pulmonary Hospital, Shanghai, China",{"id":547,"slug":548,"hasResults":11,"nctId":549,"briefTitle":550,"officialTitle":551,"acronym":4,"eligibilityCriteria":552,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":553,"enrollmentInfo":554,"targetDuration":4,"studyType":50,"phases":556,"briefSummary":557,"conditions":558,"keywords":560,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":568,"lastUpdatePostDateStruct":569,"startDateStruct":571,"completionDateStruct":573,"leadSponsor":574,"locationsCount":69},"100441846","a-study-to-evaluate-the-efficacy-of-osimertinib-with-early-intervention-srs-treatment-compared-to-the-continuation-of-osimertinib-alone-in-patients-with-egfr-mutated-nsclc-and-asymptomatic-brain-metastases-100441846","NCT05033691","A Study to Evaluate the Efficacy of Osimertinib With Early Intervention SRS Treatment Compared to the Continuation of Osimertinib Alone, in Patients With EGFR Mutated NSCLC and Asymptomatic Brain Metastases","A Multi-center, Open-label, Randomized, Two-arm Study, to Evaluate the Efficacy of Osimertinib With Early Intervention SRS Treatment Compared to the Continuation of Osimertinib Alone, in Patients With EGFR Mutated NSCLC and Asymptomatic Brain Metastases.","Inclusion Criteria:\n\n1. Newly diagnosed metastatic NSCLC, not amenable to curative surgery or curative radiotherapy.\n2. Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be sensitive to Osimertinib - These include exon 19 del; L858R (exon 21); G719X (exon 18); L861G (exon 21); S768I (exon 20) and T790M (exon 20) NOTE: Mutation analysis is to be done as per local practice.\n3. An MRI showing brain metastases. At randomization, number of brain lesions is under 20. Patients with over 20 brain lesions at randomization MRI will be suitable for whole brain radiation, and will not be randomized.\n4. Brain metastases are asymptomatic or with minor symptoms (ECOG≤2) at study randomization.\n5. ECOG performance status ≤2 and a minimum life expectancy of at least 6 months\n6. Must be eligible and receive Osimertinib as their anti EGFR TKI at time of randomization.\n7. Must be eligible for SRS treatment at time of randomization.\n8. Provided written informed consent.\n9. Be male or female and at least 18 years of age on the day of signing informed consent.\n10. Female patients:\n\n    1. Willing to use adequate contraceptive measures until 6 weeks after the final dose of study treatment\n    2. Not breast feeding\n    3. Have a negative pregnancy test prior to the start of dosing if of childbearing potential or have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:\n    4. Post-menopausal, defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation\n11. Male patients who are willing to use barrier contraception (i.e. condoms) until 4 months after the final dose of study treatment.\n\nExclusion Criteria:\n\n* a. Prior treatment with:\n\n  1. Anti EGFR TKI treatment.\n  2. Checkpoint inhibitors immunotherapy for metastatic NSCLC.\n  3. Whole brain radiation (WBRT) and\u002For Stereotactic Radiosurgery (SRS).\n  4. Medications or herbal supplements known to be potent inducers of CYP3A4 and are unable to stop use within the recommended wash out period prior to receiving the first dose of Osimertinib.\n  5. An investigational drug within five half-lives of the compound.\n  6. Any other cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of entry to the study.\n\n     b. Systemic progression under Osimertinib treatment between screen and randomization systemic scan, per RECIST1.1.\n\n     c. Spinal cord compression unless asymptomatic and stable. d. Leptomeningeal disease. e. Moderate or severe symptomatic brain metastases defined as per Radiation Therapy Oncology Group acute morbidity grade 3 to 4.\n\n     NOTE: Grade 3 refers to neurological findings requiring hospitalization for initial management. Grade 4 refers to serious neurological impairment including paralysis, coma or seizures more than three times per week despite medication and requires hospitalization.\n\n     f. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.\n\n     g. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Osimertinib.\n\n     h. Involvement in the planning and conduct of the study i. Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.","120 Years",{"count":555,"type":21},162,[81],"This study involves patients with EGFR-mutated NSCLC and asymptomatic brain metastases. This is an open-label, randomized study, comparing the continuation of Osimertinib treatment alone to Osimertinib treatment combined with early intervention stereotactic radiosurgery (SRS). The current first line of care for EGFR-mutated NSCLC is administration of Osimertinib, a small molecule that penetrates the blood brain barrier (BBB) well and controls majority, but not all, of the brain metastases. We hypothesize that relatively early intervention with SRS to brain metastases that are still visualized by MRI 2 months-post initiation of Osimertinib treatment, LUNG- will improve long term brain control, cognitive abilities and potentially overall survival. Patients with EGFR-mutated NSCLC and asymptomatic brain metastases will be treated with Osimertinib for 2 months. Brain MRI scans will be collected pre-Osimertinib and 2 months after treatment start. Patients with asymptomatic brain metastases present after 2 months of Osimertinib will be randomized into one of two study arms. Arm A patients will be treated with SRS while continuing Osimertinib, while arm B patients will continue with Osimertinib alone. Patients will be assessed based on brain and whole body progression by RECIST. Patients will also be assessed for CNS-PFS and body-PFS, cognitive function, Quality of life and overall survival status via routine follow-up tests.",[57,26,559,84,85],"EGF-R Positive Non-Small Cell Lung Cancer",[561,562,26,559,563,85,564,565,566,567],"nsclc","non-small cell lung cancer","EGFR","osimertinib","tagrisso","SRS","stereotactic radiosurgery","2021-08-30",{"date":570,"type":31},"2021-09-05",{"date":572,"type":31},"2021-03-09",{"date":356,"type":21},{"name":575,"class":38},"Hadassah Medical Organization"]